System for improving neurostimulation compliance

ABSTRACT

Nerve stimulation systems and methods are disclosed for providing improved compliance of a patient to a therapy regimen. Patient compliance is assessed and notification or treatment events can be scheduled, rescheduled or otherwise adjusted based upon patient compliance or non-compliance according to compliance rules and parameters of a treatment compliance module. Both compliance and non-compliance may lead to adjustment of the treatment regimen, scheduled treatment events, and notifications. Gamification of the treatment regimen allows users to obtain points that may be used to receive virtual awards, status awards, or monetary compensation of various forms. Monitoring of usage and compliance can be managed both locally and remotely from the user. Stimulation treatment, compliance monitoring, and gamification is disclosed for treatments using external or implanted stimulators, or the combination.

REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation-in-part of patent applicationSer. No. 15/678,824 filed 16 Aug. 2017 which claims the benefit of U.S.Provisional Patent Application Ser. No. 62/375,898 filed 16 Aug. 2016and is a continuation-in-part of patent application Ser. No. 15/160,468,which claims the benefit of U.S. Provisional Patent Application Ser. No.62/171,549 filed 5 Jun. 2015, expired, and Ser. No. 62/165,037 filed 21May 2015, expired, and claims the benefit of patent application Ser. No.14/553,427, filed Nov. 25, 2014 entitled Systems and Methods ofEnhancing Electrical Activation of Nervous Tissue which is based upon ofProvisional Patent Application Ser. No. 61/909,679, filed 27 Nov. 2013,expired; Provisional Patent Application Ser. No. 61/944,744, filed 26Feb. 2014, expired; and, Provisional Patent Application Ser. No.62/024,912, filed 15 Jul. 2014, expired.

This patent application claims the benefit of U.S. provisional patentapplication Ser. No. 62/608,540 filed 20 Dec. 2017.

INCORPORATION BY REFERENCE

This patent application hereby incorporates by reference, U.S. patentapplication Ser. Nos. 15/678,824, 15/438,415, 15/160,585, 15/160,468 and14/553,427, and U.S. Patent Applications Ser. Nos. 61/909,679,61/944,744, 62/024,912, 62/165,037, 62/171,549, 62/375,898, and62/608,540 which are hereby incorporated by reference in entirety forall purposes.

FIELD

The subject concept relates to the field of modulating biologicaltissue.

BACKGROUND

Nerve stimulation (neurostimulation) technology includes applicationssuch as electrical neuromodulation, functional electrical stimulation,and therapeutic electrical stimulation. Nerve stimulation is aneffective clinical tool used to treat various chronic medical disordersand conditions. Examples include (1) deep brain stimulation (DBS) fortreating Parkinson's disease and essential tremor, (2) spinal cordstimulation for treating pain and voiding disorders, and (3) peripheralnerve stimulation for treating pelvic floor disorders and dysfunctions(e.g., overactive bladder), pain, obstructive sleep apnea, headache,migraine, epilepsy, depression, hypertension, cardiac disorders, andother disorders and disease states. Peripheral nerves may include, forexample, the vagus nerve, occipital nerve, cranial nerves, spinalnerves, pudendal nerves, cutaneous nerves, and the sciatic and femoralnerves.

The peripheral nervous system provides a neural substrate that allowsnerve stimulation to treat various disorders. Long-term viability ofimplanted neurostimulators can be complicated by issues related torepeated mechanical movement (e.g., lead fracture and/or componentmigration). Transcutaneous electrical nerve stimulation (TENS) canprovide a more simple and non-invasive approach. However, selectivenerve activation by TENS may not be readily achieved due to, forexample, intervening tissue or distance between a nerve target and theskin surface. Accordingly, some therapies rely on percutaneousstimulation to stimulate a target nerve.

Advances in minimally-invasive nerve stimulation have been realizedclinically. Wireless implantable electrode probes have been developedfor achieving less invasive methods of selective nerve stimulation. TheBION (Advanced Bionics) is a glass or ceramic covered electrode that canbe percutaneously injected into a region of interest. It can beself-powered or passively charged by radio frequency (RF) pulses.Long-term use may be complicated by migration of the BION from itsoriginal implant location. This migration may cause both reducedtherapeutic effects and increased stimulation-evoked side effects due toactivation of other (non-target) tissue. Nerve stimulation systems(e.g., MicroTransponder Inc. SAINT™ System) which are smaller, lessexpensive, and/or less technically complicated than the BION may beadvantageous in treatment of some disorders. StimGuard has developedinjectable implantable neurostimulators, which use wireless power in theRF and/or microwave frequency rage and non-inductive antennas whichreceive electromagnetic energy radiated from a source located outside ofthe patient's body. Energous technology is developing wirelesstechnology that utilizes multiple antennae to provide improvedtransmission and harvesting of wireless energy and is developing withinthe implantable device space. These innovative technologies will allowsmaller form factors. Witricity is using wireless magnetic inductiontechnology to power implanted devices. Alternatively, ValenciaTechnologies has developed a coin-shaped implantable neurostimulatordisclosed, for example in US App Nos. 20140214128A1, US20140214144A1,US20150148864A1, (all to Peterson et al.), which has a battery which maynot be rechargeable, and which can last 2-3 years when providingperiodic stimulation for disorders such as overactive bladder.

Transcutaneous magnetic stimulators (TMS), termed “transcranial magneticstimulators” when used for brain stimulation, are used to treatdisorders such as migraine (e.g. those made by Neuralieve Inc. such asU.S. Pat. Nos. 7,294,101, 8,262,556) by using an external magneticstimulation device to stimulate central or peripheral tissue targets.The fields induced inside the tissue by one or more pulses (e.g., suchas may occur with pulsed electromagnetic stimulation) may be lesslocalized than desired. The present invention may offer advantagesrelated to enhancing the effects of externally applied magnetic and/orelectrical fields near a target nerve.

In addition to pain treatment, TENS systems have been used to applyelectrical fields to the brain to modulate sleep, anxiety, depression,pain, attention, memory, and various types of brain activity. TENSsystems are being developed to enhance performance of athletes bystimulating a person's head, although the mechanisms of action are notfully understood. TENS is not currently used to reliably treat certaindisorders such as overactive bladder. This may be due, at leastpartially, to the difficulty of modulating the posterior tibial nervewhich may be too deep for sufficient portion of the TENS signal tomodulate the nerve target. The disclosed systems and methods may allow aTENS system to stimulate novel anatomical areas and nerve targets in thetreatment of overactive bladder.

The first largely available percutaneous nerve stimulation method andsystem for treatment of overactive bladder was provided by Uroplastyunder the name “Urgent PC”. The therapy involves posterior tibial nervestimulation using a percutaneous needle electrode at a site above andposterior to the patient's medial malleolus which stimulates inconjunction with an electrode attached to the medial side of a patient'sfoot. The method and system has been described in U.S. Pat. Nos.6,493,588, 7,668,598, 8,046,082, 8,812,114, 9,056,194, 9,265,941assigned to Uroplasty. The Urgent PC system design incorporates a “use”status when the device is ready to provide therapy and a “do not use”status when the device is not ready. The device works with a lead sethaving a status flag element with a “use” status which converts to a “donot use” status at a predetermined time after starting the therapy. Thestatus change includes blowing a fuse of the lead set so that the leadcannot be re-used for subsequent therapy. Single-use leads require a newlead must be purchased and used for each subsequent provision oftherapy.

A more recent alternative percutaneous nerve stimulation method andsystem has been described in U.S. Pat. No. 8,660,646 entitled“Percutaneous tibial nerve stimulator” to Laing et al. The disclosuredescribes a system developed by Advanced Uro-Solutions and nowdistributed under the name NURO by Medtronic. The system uses a methodthat includes providing a computer system having a customer interfaceand a neurostimulator unit that is operated in conjunction with theinterface. The neurostimulator contains a pulse generator that iselectrically coupled to a transcutaneous electrode configured to beapplied to skin of a patient (e.g. inner foot) and a percutaneouselectrode for insertion at stimulation site of a patient which is theposterior tibial nerve. A microcontroller communicates with the pulsegenerator and allows for the monitoring of how many treatment creditsare available to be used by the neurostimulator. If there is at leastone treatment credit, the microcontroller allows for activating thepulse generator and decrements the treatment credit counter when atreatment is provided to a patient. The system also provides for acomputer system that can receive a treatment credit request transmittedthrough the customer interface and adjusting the number of treatmentcredits available based on the number of treatment credits purchased.Accordingly, the system allows for treatment to be accomplished if thetreatment has been paid for by obtaining a treatment-credit beforehand.

These prior art systems suffer limitations. These provide a singlestimulator (e.g., configured to provide a single percutaneous electrodefor insertion at a single treatment site near the ankle). More than onestimulation site may be beneficial and stimulating the saphenous nervenear the knee may have advantages. Stimulation systems may not allow forproviding more than one treatment across an interval (e.g., 3- or24-hours) although all treatments may be related to a single event ordisorder, but with greater severity, requiring a larger “dose”. Forexample, treatment credits are related to a single stimulation sessionlasting a defined duration.

The prior art percutaneous stimulation devices for treatment of OAB bystimulation of the posterior tibial nerve (PTN) suffer additionaldisadvantages and limitations. For example, they are designed forpercutaneous stimulation of the PTN rather than for percutaneous ortranscutaneous stimulation of the saphenous nerve, or for a combinationof different stimulation methods (e.g., first percutaneous and thenTENS, using a combination of external and implanted neurostimulators).

Another disadvantage is that prior art stimulators are not configured toadjust stimulation parameters for, and then provide stimulation with,signals provided at two or more percutaneous stimulators that areapplied to the patient to provide stimulation of targets including, forexample, both the PTN and the saphenous nerve (SAFN). There is noprovision for display of different stimulation parameters related to twoor more targets.

Another disadvantage is that prior art stimulators (e.g. percutaneous,magnetic, etc) used for treatment various conditions implement apay-per-session paradigm. For example, in the treatment of OAB (ormigraine) there is a charge to stimulate at a single stimulation site.This does not allow for stimulation using 1 or more neurostimulators orfor nerve stimulation using needles at two stimulation sites. This alsodoes not allow for requiring payment to activate a device for a singleinterval of use rather than for each of a plurality of uses within thatinterval (e.g. several therapy sessions on a single day).

Another disadvantage is that prior art TENS stimulators (which workeither jointly, with or without, implanted components) are notconfigured to provide treatment related to overactive bladder withfeatures that promote compliance and therapy benefit. Prior art TENSstimulators are also not configured to provide stimulation of thesaphenous nerve in the treatment of overactive bladder or other pelvicfloor disorder.

Systems and methods are needed which provide advantages for bothclinic-based and home-based therapy such as one or more of thefollowing: a) providing at-home stimulation treatment to patientscontingent upon a subscription being valid; b) allowing for providing aselected number of treatments within the course of a selected, andprogrammable, treatment window such as a 6, 12, 24 or 48 hour period, oran interval of weeks or months; c) monitoring, recording, displaying,reporting, sending and operating upon usage data related to treatmenttimes, durations, compliance, non-compliance, and other characteristicsof patient use; d) alerting doctors, caregivers, or patients to promotecompliance and/or when non-compliance or incorrect-use occurs; e)providing the selection of session-based, dose-based, interval-based,local-based and remote-based use-management; f) providing TENS systemsconfigured for OAB treatment and/or stimulation of the saphenous nerveto provide treatment of other disorders or provide other benefit; and g)providing a gamification system that increases the fun and entertainmentvalue of the treatment, augments compliance, and rewards the user forproviding treatment in the intended manner.

SUMMARY

In an embodiment, a transcutaneous tissue stimulation system and methodis provided which includes one or more electrical generators positionedexternal to a patient. Stimulators which are either needle or TENSelectrodes are electrically coupled to the one or more electricalgenerators and are positioned on the surface of, or penetrate, thepatient's skin. Multiple target nerves may be defined with differentstimulation protocols as part of the treatment program.

In embodiments, systems and methods are provided for achieving effectivetherapeutic nerve activation of the SAFN with TENS of the medial portionof a patient's leg between approximately the knee and the medialmalleolus which can enable a primarily home-based TENS therapy treatmentfor OAB to become a simple (e.g. first-line) treatment option similar tolifestyle changes, or a second line treatment option to be used ratherthan drug therapy, since this does not require ongoing, frequentclinic-visits for percutaneous intervention.

In embodiments, stimulation systems and methods are described forproviding advantages related to increasing therapeutic efficacy of nervestimulation, improving the comfort of a patient relative to alternativetherapeutic solutions, increasing patient compliance, decreasing thecost of treatment, and/or providing for a simple treatment usingexternal and/or implanted components.

In embodiments, an implanted, electrically conductive member ispositioned on, or contiguous to, a target nerve tissue for stimulationof the target nerve tissue to modify the electrical field signalsgenerated by the electrical generator and provided by the stimulator forthe purpose of modulating signals from the nerve tissue to the brain, tothe central or peripheral nervous system, or other target, of thepatient. System and methods aim to avoid activation of non-targetednervous tissue, which can both limit the overall therapeutic effects andexacerbate stimulation-evoked side effects. The implanted passiveelement is configured to allow therapy to achieve the same, or improvedtherapeutic benefit as that which would otherwise be achieved when usingonly transcutaneous nerve stimulation without an implanted passiveelement. The systems and methods for providing stimulation of tissueusing complementary or “paired” configurations of external stimulationelements and subcutaneously implanted passive elements.

Another objective is to provide systems and methods for achievingeffective therapeutic nerve activation with relatively lower stimulationamplitude and/or shorter pulse width than what is typically achievableusing prior art methods (e.g., TENS).

While the systems and methods disclosed herein are generally orientedfor peripheral nerve stimulation, these may also be applied tostimulation of other targets of the spine, brain, or body.

These and other objectives and advantages of the invention will now bedisclosed in the figures, detailed description, and claims of theinvention.

In the illustrated embodiments, any steps shown in the figures may occurin a different order, may be repeated, may lead to different steps ofthe method shown within each figure, or may lead to steps shown in otherfigures. Steps and components shown may be included or excluded from aparticular embodiment, and this may occur conditionally, or according tothe system or treatment protocol implemented by a therapy program. Thetherapy program may be implemented partially or fully by one or moreprocessors of a medical system which may include an external, or apartially or fully implantable neurostimulator. The therapy program canbe adjusted according to control by, or therapy plan implemented by, apatient, doctor, remote medical service, or caregiver.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a view of a neurostimulation system applied to a patient forstimulating the saphenous and posterior tibial nerve targets accordingto an embodiment of the invention;

FIG. 2 is a view of a neurostimulation system having two neurostimulatordevices applied to portions of separate legs of a patient according toan embodiment of the invention;

FIG. 3A is a view of a neurostimulation system having twoneurostimulator devices applied to two portions of a single leg of apatient according to an embodiment of the invention;

FIG. 3B is a view of a TENS electrode linking system for linking theTENS circuits of two neurostimulator devices according to an embodimentof the disclosure;

FIG. 4 is a view of a neurostimulation system applied to a leg of apatient for providing percutaneous stimulation according to anembodiment of the disclosure;

FIG. 5 is a view of a neurostimulation system applied to a leg of apatient for providing transcutaneous stimulation according to analternative embodiment of the disclosure;

FIG. 6A is a view of target locations for a neurostimulation systemapplied to a back of a patient for providing transcutaneous stimulationaccording to an alternative embodiment of the disclosure;

FIG. 6B Shaded anatomical plot of the sensation perceived during SAFNstimulation, showing that as the amplitude was increased from thresholdskin (T-skin) to threshold where discomfort was experienced (T-limit),the evoked sensation spread across the entire medial aspect of the lowerleg, down to the ankle (N=15 subjects).

FIGS. 7A and 7B show two displays related to patient compliance that canbe provided by a compliance module of a neurostimulator system.

FIG. 8 is a schematic diagram of a neurostimulator system and functionalmodules which may be used to realize embodiments of the currentinvention including the provision of tissue stimulation.

FIG. 9 is a schematic block diagram of circuitry that supports thefunctional modules of an embodiment of a neurostimulator system.

FIGS. 10A and 10B are views of example displays that serve as userinterfaces in an embodiment of the system.

FIGS. 11A,B,C show alternative TENS accessories and embodiments for usewith the current invention.

FIG. 12 shows a flow chart of a method for providing therapy.

FIGS. 13A and 13B show additional flow charts of a method for providingtherapy.

FIG. 14 shows a TENS system having an electrode array and aneurostimulator.

FIG. 15 shows a top and bottom portion of a neurostimulator.

FIG. 16 shows an example of a method for assessing compliance andcontingently adjusting treatment events and operations.

FIG. 17 shows an example of a look-up table related to treatment regimenevent parameters.

FIG. 18 shows an example of a look-up table related to notificationparameters and rules.

FIG. 19 shows an example of a method related to gamification of atreatment regimen.

FIG. 20 shows an example of a look-up table related to gamificationpoints.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Reference will now be made in detail to exemplary embodiments of thepresent disclosure, examples of which are illustrated in theaccompanying drawings. Where possible, the same reference numbers willbe used throughout the drawings to refer to the same or like components.When titles are provided for different sections of this disclosure theseare merely to highlight certain themes and are not meant to limit theinvention concept.

FIG. 1 shows an embodiment of neurostimulation system 10 applied to apatient for stimulating one or more targets in the leg of a patient 6which in this example are a saphenous nerve target and posterior tibialnerve target. The neurostimulator 50 has a housing 12 and a power button14 for turning the device on and off. A set of dedicated buttoncontrollers 16 (labeled 1, 2, and 3 in the figure) provide functionalitysuch as for starting stimulation (e.g. beginning a treatment sessionthat will last a selected time interval), pausing stimulation, andhalting stimulation. The “pause” function can allow the therapy to bepaused and restarted within a specified interval after the stimulationis started without blowing a fuse of the electrode lead set (Uroplastytype system) or decrementing the treatment credit (Nuro type system).This can allow for the needle to be repositioned if needed. A menucontroller 18 operating in conjunction with the user interface module 80allows a user to navigate through a set of menu options presented on thedisplay 20 to select and/or adjust operation of the system 10. Forexample, a user can adjust a therapy protocol parameter such as theamplitude of at least one stimulation signal that may be selectivelyprovided to one, two, or more stimulators such as a first and secondpercutaneous needle electrode 28 a, 28 b. The display 20 is configuredto present a user with information about stimulation parameter valuesrelated to stimulation of at least a first target (e.g. SAFN) and also asecond target (e.g. TN) when two or more stimulation targets aremodulated during therapy for overactive bladder or other disorder.

A conduit connector 22 is formed as a plug that connects theneurostimulator 50 to a lead set 24. In an embodiment, the lead setconnects to a first lead 84 which connects to a surface stimulator TENSelectrode 88 and a second lead 86 which is multi-stranded and branchesinto individual wires 86 a and 86 b, which may be single ormulti-stranded, and which provide the stimulation signals to two needleelectrode clips 26 a, 26 b. In an alternative embodiment, stimulation isonly delivered to the SAFN and a single wire 86 b, clip 26 b, and needleelectrode 28 b are provided. In other words, lead set 24 can communicatethe stimulation signal to the TENS electrode 88 and only to one needleholder 26 b, when only 1 percutaneous needle stimulator is used. Thesystem 10 may also be designed so that stimulation signals travelbetween the two needle electrodes 28 a, 28 b and a TENS electrode 88 isnot provided.

In the illustrated embodiment, needle electrode 28 a is insertedpercutaneously at a first location cephalad and posterior to the medialmalleolus, while needle electrode 28 b is inserted at a second locationto stimulate the SAFN, such as a location cephalad and anterior to themedial malleolus. The surface electrode 88, is positioned on the medialsurface of a foot of a patient 6 (other locations below or above theankle are also viable).

The display 20 shows a setting of “6”, reflecting amplitude or strengthof the stimulation signal applied at needle electrode 28 b for “SF”(i.e. SAFN) stimulation, while “10” reflects amplitude of stimulationapplied at the PTN site. The user has selected a stimulation protocolparameter value of “Same” which indicates that the stimulation issupplied to the SAFN and PTN at the same time, rather than “Alt” whichwould cause the sites of stimulation therapy to alternate. Alternatingmay include, for example, periodically stimulating for 5 minutes at thefirst target site followed by 5 minutes at the second, and so on.Alternating can also include stimulating at 10 Hz at both SAFN and PTN,with two stimulation signals that are time lagged to be out of phasesuch that the combined signal of the 2 interleaved series of pulses is20 Hz.

The display 20 can also indicate additional information such as a timervalue showing the duration of the therapy that has occurred (or theduration remaining), remaining battery charge, stimulator and/or sensorimpedance values, errors or faults (e.g., the neurostimulator did notreceive a scheduled maintenance or calibration). Information aboutwireless data and/or power communication strength (or connectionstatus), related to communicating power or data signals betweendifferent component of the neurostimulation system 10 and/or theneurostimulator 50 may also be shown. In addition to the display 20, theneurostimulator 50, can also use LEDs 92 a/156 (e.g. see FIG. 6, andFIG. 11B) situated on the housing 12 in order to indicate a status of ameasure such as impedance (e.g. green=good) or to alarm/alert the userabout the status of therapy or device operation. The display 20 can bemuch larger than that shown in the figure, and may be supplied on a userprogrammer 70 to enable clear presentation of graphs and tables relatedto usage and compliance. In an embodiment, the display 20 can alsodisplay treatment credit information.

In alternate embodiments, either the graphic display 20 or some of theuser interface controllers may be realized as detachable from theneurostimulator housing 12. For example, the neurostimulator 50 may becontrolled by a user who has established wireless communication linkbetween it and a smartphone, tablet, laptop or other device, that mayserve as type of user programmer 70 (which is a device such as acomputer having a control module with controller circuitry such as aprocessor, display, memory, power source, communication means, and othercircuitry as is well known, see FIG. 2). Remote controlling of thedevice 50 can be provided in addition to, or as an alternative to, theuser input buttons 18 and display 20 on the housing 12. Theneurostimulator 50 can communicate using wireless signals (e.g.,infrared, Bluetooth, WIFI) or by wired connection, and can send dataover the internet. A user's laptop can be provided with a softwareapplication that provides instructions to a processor for linking with,and subsequently control of, at least one neurostimulator 50 as well asserving as a display/controller device. Either the neurostimulator orthe linked device can operate to notify a user (patient oradministrator) by sending a visual, sonic, or other alert signalindicating a status or parameter value related to the provision oftreatment using the user interface module 80 and related alertingcomponents 156.

In an embodiment, a stimulation signal with a fixed frequency (e.g., 20Hz and a pulse width of 200 usec) is increased until a behavioralresponse is seen such as flexion of the big toe or fanning of all toesbecomes visible, or until a subjective response is made (e.g., tinglingsensation is reported radiating towards the foot or toes). However, insome patients, such as those with diabetes and various neuropathies, asubjective report may not be accurate or subjects may be unsure ofwhether a nerve is being stimulated for various reasons. According to anembodiment of the present invention, using sensor data enables thedetection of a quantitative measure such as a motor evoked response. Inan embodiment, a second connector 23 connects the neurostimulator 50 toa lead set 85 which connects to at least one sensor such as a disposableTENS surface electrode 88 b. In order to monitor nerve or muscleactivity (e.g., EMG), the TENS electrode 88 b can be realized with twoelectrical contacts. Alternatively, two disposable TENS surfaceelectrodes can be attached to the lead set 85. The neurostimulator 50 isconfigured to provide sensing and evaluation of a signal related to theprovision of therapy, such as an EMG signal, using the sensing andprocessing modules 55, 58 to detect a person's foot muscle activation(e.g., toe flexion or extension) in response to the stimulation of thePTN. Alternatively, measuring “muscle twitch” activity could occur usinga sensor (e.g. strain gauge or wearable electrode) embedded with a sockor realized in an adhesive band-aid like form factor (which may looklike a surface electrode with one or more embedded strain gauges and usea bonded metallic strain gauge design on a flexible backing). Flexion ortwisting of the strain gauge will cause change in voltages that signalsefferent activation.

FIG. 2 shows an alternative embodiment of a neurostimulation system 8for stimulating a first and a second nerve target in a first and secondleg of a patient. In this case the first target is an anterior branchSAFN target on the first foot (left side of figure) and the second is aPTN target on the second foot (right side of figure). A first and secondneurostimulator 51 b, 51 a are configured to provide stimulation to theSAFN via first needle stimulator 28 b and PTN using second needlestimulator 28 a (the end of the conduit 86 can be attached to a needleholder which, in turn, attaches to the needle 28, as in FIG. 1, but thisis not shown to avoid cluttering of the figure). As shown, the front(i.e., “top”) surface of the neurostimulator has displays and buttons.The neurostimulators connect with the patient through a disposable TENSelectrode 88 a, 88 b that can be attached to the back (i.e., “bottom”)surface of each neurostimulator 51 a, 51 b (e.g. the electrode can snaponto an electrically conductive snap on the back side of thestimulator). Attachment of both neurostimulators to the patientcompletes the stimulation circuit for each foot. This configuration maybe useful, for example, in patients who are receiving stimulationtherapy for both the SAFN and PTN, but who have trouble tolerating (orhave difficulty in being able to distinguish or assess) stimulation ofboth targets in the same leg. In an alternative embodiment, stimulationis only delivered to the SAFN of both the left and right leg byneurostimulators 51 a,51 b.

Although a neurostimulator 51 b and its associated lead set 86 can bedesigned to provide stimulation of two or more stimulators 28 (as shownfor the system 10 of FIG. 1), there may be manufacturing and regulatoryadvantages to use a neurostimulator design that has already beenapproved by regulatory agencies for stimulation of a single site on oneleg and also factors related to patient comfort. Additionally, usingneurostimulators that have hardware, software, and protocols designedfor stimulation of a single site may be easier than designing a morecomplicated stimulator and user interface to stimulate more than onenerve target using a single stimulator. For at least these reasons, thesystem 8 can use neurostimulator embodiments that provide for jointoperation of, and/or connection between, two or more neurostimulators.

When two neurostimulators 51 a, 51 b use a pay-per-use, orpay-per-therapy-session, or other treatment-credit-based system, then atherapy protocol which includes stimulating two different targets insingle patient may require certain features to avoid problems that wouldotherwise occur. For example, although two stimulators are being usedduring a single treatment, it may not be desirable or appropriate tocharge for two different treatments and decrement the treatment creditsby 2 rather than 1. Several solutions are provided by the systems andmethods disclosed herein. In an embodiment a user/physician programmer70 may communicate in a wired or wireless manner with the payments andpermissions modules 202 of the first and second neurostimulators 51 a,51 b such that both neurostimulators can be activated to provide atreatment but only one neurostimulator will have its treatment creditvalue decreased. In the figure the neurostimulator on the right side ofthe figure has had its credit reduced by 1, to 15, while theneurostimulator on the left remains at 16 credits during the provisionof the current treatment. Alternatively, the user/physician programmer70 may be responsible for management of the treatment credits and sendsactivation codes to the neurostimulators 51 a, 51 b which simply obtainpermission from the user/physician programmer 70 to provide treatment.Alternatively, one of the first and second neurostimulators 51 a, 51 bis designated a ‘Master’ device while the other is designated a ‘slave’.The designation can be implemented using either hardware or software orboth, and may be realized as part of the payments and permissions module202. For example, the master device keeps track of the payment creditsand the slave device is controlled by the master device, and may not beused or controlled in the absence of the master device. In analternative embodiment, a patient-specific tag signal (e.g., a lowamplitude sinusoid modulated by a combination of two or more frequencycomponents and one or more silent periods) can be transmitted by onestimulator and must be sensed by a second stimulator to ensure the twostimulators are attached to the same person. The signal is transmittedand received wirelessly using near range communication by thecommunication modules 68, or is transmitted by one stimulator 51 athrough the patient tissue and sensed by the other stimulator 51 b,whose sensing module 55 is configured to detect this signal. Using atreatment credit system for payment may be more easily applied tostimulation of 2 or more sites since using a needle stimulator with afuse increases the cost of treatment when 2 sites are used.

In embodiments, various limitations may be imposed by the payments andpermissions module 202 to deter fraudulent treatment of two patientswhile only being charged for 1 treatment. For example, both stimulatorscan be simultaneously activated to provide therapy, but an operationlimitation requires that the start of therapy must occur within 5minutes of a communication session with the user/physician programmer 70for both a first and second neurostimulator 51 a, 51 b. Alternatively,the first and second stimulators 51 a, 51 b can be required toperiodically attempt communication with each other during the provisionof a therapy session and if this is not successful (e.g., for at least 1of 4 attempts) then it may suggest that the devices are being used in 2locations with 2 different patients. If this requirement was not met,then the system 8 can be designed so that the “activation” of at leastone of the two neurostimulators is halted so that it does not providetherapy or an alert signal is sent indicating that the two devices arenot communicating correctly. Wired or wireless communication can beprovided by the communication modules 68 of the neurostimulators, andalso of the programmer 70. A near field wireless technology can be usedto establish a communication channel that allows for approximately only,for example, a 1 to 2 foot range for communication in order to ensurethat the two neurostimulators are in close proximity. Additionally, aconduit 90 such as a microUSB, or custom, cable can be inserted into oneof the I/O ports 114 a of each neurostimulator, and the twoneurostimulators can communicate in a wired manner to allow the therapyto be delivered using the appropriate allocation of a single treatmentcredit.

The neurostimulators 51 a, 51 b and a user/physician programmer 70 cancommunicate to transmit data and/or power signals to each other. Theuser/physician programmer 70 can, in turn communicate with a remotemanagement computer 71, and can relay communication between other system8 components. The management computer 71 may be at least one computer,or part of a network of computers that operate software instructionsunder control of their processors to manage aspects of the therapy suchas purchase and delivery of payment credits and/or recording, assessing,and reporting data related to times and durations when therapy wasprovided. The management computer 71 can set flags and operationalvalues related to use, payment, and compliance, as well as otherrelevant data. In an embodiment the user/physician programmer 70 cancommunicate with a remote management computer 71 to transmit a signalover a computer network to submit a request for one or more treatmentcredits with associated reimbursement codes that are related toproviding stimulation using either one neurostimulator or more than oneneurostimulator (or one stimulator which is being used to treat one ormore sites). In the latter case, in an embodiment, the remote managementcomputer 71 can provide the user/physician programmer 70 with therapycredit that is designed to allow for the activation of twoneurostimulators to be used in treatment of a single subject. Inadditional embodiments, rather than one or more neurostimulators keepingtrack of the therapy credits, the user/physician computer 70 can managethe treatment credit usage. For example, the user/physician computer 70can provide an activation code signal to the two or moreneurostimulators and then operate its processor to decrease thetreatment credit value stored in its own payments and permissionsmodule. For tracking purposes each treatment credit may have a unique IDvalue. The ID value may contain fields for information about when,where, and how the credit was purchased and/or used. The ID valueaccordingly may have a plurality of fields, some of which are modifiableby a programmer or neurostimulator.

In an embodiment, when the neurostimulators 51 a, 51 b are used in thesetting of a patient's home or are otherwise used outside of a clinicsetting to provide therapy stimulation then the user/physicianprogrammer 70 can communicate with the neurostimulators 51 a, 51 b andwith a remote management computer 71 that manages aspects of thetherapy. This is true regardless of whether the therapy is at least oneof: transcutaneous (e.g., via electrical, vibratory, magnetic, or othermodality), occurs under control of an external device that providescontrol and/or power of an implantable device that provides therapy,occurs by the programmer 70 communicating with an implantable device toadjust the operations relate to therapy, or otherwise. Additionally, theuser/physician programmer 70 in a patient's home may communicate with aremote physician programmer 70′ at the patient's physician's officewhich may, in turn communicate with the remote management computer 71 inorder to manage the patient's therapy. In other words, the physicianprogrammer 70′ at the physician's office can act as a relay between theuser/physician programmer 70 at the patient's home and the managementcomputer 71. The management computer 71 may be operated by a medicalcompany that charges users or doctors for ongoing use, per-treatmentuse, time-based rental, purchase, and/or periodic activation of theneurostimulators for selected intervals of time (e.g. 1 hour or 1month). The management computer 71 may in turn send and receiveinformation with computers of insurance companies in order to carry outoperations related to insurance monitoring and reimbursement. Ratherthan a user programmer 70 communicating directly with a medical companyor insurer, a clinic may prefer the user programmer 70 to communicatewith the physician programmer 70′ at the clinic, which in turncommunicates with the management computer 71. This indirect route ofsending data over a computer network, by routing information through theclinic may be preferable for the clinic (who may wish to charge ormonitor user treatment) and also for a medical company that may choosenot to directly communicate with or receive data from patient devices.Additionally, during a periodic exchange of data related to devicepayment, data relating to device use (stimulation times, durations, andstimulation parameters) can be exchanged. The transmission of user datafrom user devices to a physician programmer 70′ may provide a doctorwith the opportunity to review the usage of a particular patient ratherthan requiring this information to be acquired during a patient visit.In some instances, this may reduce the need for more frequent patientvisits. In an embodiment, user compliance data (e.g. whether a patientsuccessfully self-stimulated at least a minimum number treatmentsessions per week) can be at least periodically communicated with eithera doctor's office (e.g. management computer 71) or an insurance companyor both. The management computer at remote site can be a computer thatis managed by an insurance company, or the management computer 71 may bepart of, or communicate with, a network of computers operated by areimbursement stakeholder.

When a needle-type electrode is used to percutaneously stimulate thesaphenous nerve, it may be constructed using an electrically-insulatingmaterial that has an electrically-conductive contact located at thedistal tip. Such a design would reduce the electrical activation ofnervous tissue at the skin and minimize discomfort or pain felt by thepatient in this area. In an embodiment, a pulse generator of astimulation module 54 of the neurostimulator 50 is electrically coupledto both an electrode TENS pad 88 and a percutaneously inserted needleelectrode 28 b for stimulating the SAFN. During stimulation treatment,current pulses of the stimulation signal traverse the stimulation siteby passing from the TENS electrode 88 to the conductive portion of theneedle electrode 28 b. Additionally, the subject system can beconfigured to operate a needle stimulator with two contacts (e.g.,conductive annular rings) formed on an insulated needle that serves as abipolar electrode. In an embodiment, two conduits can connect to twocontacts on the top of the needle stimulator which respectively connectto the first and second annular ring. The needle does not need to beconductive and can be made of plastic or other suitable non-conductivematerial that has electrical routing disposed along its length providedby conduit means. When two needle electrodes are used on the same foot,the current pulses can pass between a TENS electrode and each needleelectrodes 28 a, 28 b (see FIG. 3A). Alternatively, when two needleelectrodes are used to achieve bilateral nerve stimulation, the currentpulses can pass between each respective pair of TENS electrodes andneedle electrodes 28 a, 28 b. In some stimulation protocols, the TENSelectrode 88 and the needle electrodes 28 a, 28 b are designated asanode and cathode, respectively, while in others these designationschange over time. In an embodiment, the TENS electrode is not used, andthe current pulses can travel between the two needles 28 a, 28 b.

FIG. 3a shows an embodiment of neurostimulation system 8 applied tostimulate a first and a second target in the same foot of a patient 6. Afirst and second neurostimulator 51 b, 51 a are configured to providestimulation to the SAFN using needle stimulator 28 b and PTN usingneedle stimulator 28 a. A disposable TENS electrode 88 a is connected tothe bottom surface of neurostimulator 51 b to complete the stimulationcircuit with needle stimulators 28 b, 28 a. There may not be sufficientsurface area on the medial side of a patient's foot for bothstimulators. Further due to patient comfort, or for other reasons, it isnot preferable for the second neurostimulator to be placed elsewhere onthe patient. Accordingly, a neurostimulation linking system can berealized using a communication cable 90 which connects to I/O connectors114 a provided in the housing 12 of each neurostimulator (see FIG. 2).In an embodiment, I/O connectors 114 a connect to various components ofthe neurostimulators 51 b, 51 a including a circuit 145 (see FIG. 9)that electrically joins the circuitry of the stimulation module thatconnects to the TENS electrode used for the neurostimulator 51 a, to theelectronics connected to the TENS electrode 88 a of neurostimulator 51b. This allows the disposable TENS electrode 88 a of the firstneurostimulator to serve as the return path for the secondneurostimulator as well. The neurostimulation linking system can also bedesigned to enable data signals sent using wires of the communicationcable 90 such as those related to the operation of the payments andpermissions modules 202 of both neurostimulators. Communication cable 90enable the modules of the two systems to collaborate to providestimulation while also managing treatment credits appropriately (e.g.,decrementing the treatment credits of only 1 of the neurostimulators dueto the provision of a single therapy session).

An alternative system and method of connecting the two neurostimulators,which also does not require the second neurostimulator to be attached tothe patient's foot, is shown in FIG. 3b as a TENS electrode linkingsystem. In this example embodiment, two disposable TENS electrode padscan be attached via their electrically conductive snaps 89 a,89 b to thebottom of the two neurostimulators 51 a, 51 b as would typically be donewhen providing therapy to a patient. The first TENS electrode pad 88 bhas a bottom side that makes contact with the patient's skin and a topside that snaps onto the first neurostimulator 51 b to provideelectrical connection from the neurostimulator to the patient's skin.The first TENS electrode pad 88 b also has a connector for connecting toa second TENS electrode via a linking cable 91. The secondneurostimulator 51 a also has a TENS electrode pad 88 a that can then beelectrically and physically connected to the first TENS electrode pad 88b by a linking cable 91. In this embodiment, the second TENS electrodepad 88 a is not attached to the patient and therefore does not requireits bottom surface to be adhesive or electrically conductive, althoughit can be. In an embodiment, the second TENS electrode pad 88 a isrealized simply as a snap-type connector that snaps to the bottom of theneurostimulator 51 a and connects to cable 91. Alternatively, when onlyone neurostimulator 51 b is used, it may be designed to connect toelectrode pad 88 b to provide stimulation to a patient's skin, and mayhave 2 stimulation channels for stimulating at 2 different needleelectrode sites, both of which are commonly referenced to the pad 88 b.

FIG. 4 shows an embodiment of a neurostimulation system applied to a legof a patient 6 for providing percutaneous stimulation. Theneurostimulator may be configured to provide stimulation of the SAFNusing needle stimulator 28 b at a first location near the knee—at aposition 2-3 inches distal to the knee and on the medial surface. Morespecifically, the SAFN can be targeted by inserting a 34G needleelectrode within a ‘notch’ region located between the medial condyle ofthe tibia and the superior border of the medial gastrocnemius muscle. Itis oriented in the anterior-posterior direction and has a width ofapproximately 1.5 cm. In a group of OAB patients the notch provided aneasily identifiable and reliable region for providing SAFN therapy withpercutaneous stimulation. Each patient could confirm activation of theSAFN by sensing electrotactile stimulation (paresthesia) radiating downtowards the ankle, and even into their foot (MacDiarmid, John and Yoo Apilot feasibility study of treating overactive bladder patients withpercutaneous saphenous nerve stimulation). Further in this study wefound a robust treatment response with patients showing improvements inmultiple bladder symptoms which appears clinical effective in thecontext of changes typically seen with OAB therapeutics. In a system andmethod of the current invention, this notch area is used to providestimulation, or users are instructed to use locations within this area.Additionally, or alternatively, stimulation may be provided using needlestimulator 28 c at a second location cephalad and posterior to themedial malleolus to electrically target the PTN. A TENS electrode 88placed on the medial aspect of the foot (or between the two electrodes,near the tibia at about the level of mid-calf, not shown) may be used tocomplete the stimulation circuit in the case where one or more needlestimulators are used. Alternatively, the stimulation pathway may bedefined simply by using the first and second needle electrodes 28 b,28c. Additionally, the first needle electrode and the TENS electrode nearthe calf may define one circuit and the second needle electrode 28 c andthe electrode 88 may define a second stimulation circuit. Stimulation ofthe SAFN using a needle electrode near the knee has been previouslyshown as a means of guiding the percutaneous injection of lidocaine forachieving nerve block of the foot (Benzon et al. Comparison of thedifferent approaches to saphenous nerve block. Anesthesiology. 2005March; 102(3):633-8). Accordingly, methods for determining the locationof the SAFN have been successfully practiced using imaging modalitiessuch as fluoroscopy, ultrasound, and/or electrical stimulationtechniques, which can also be incorporated into the currently disclosedtherapy for overactive bladder or other disorder. Alternatively,however, subjective responses such as tingling (paresthesia) radiatingaway from the electrode and along the medial aspect of the lower legbeing reported by a subject can be used to select and confirmappropriate locations for electrically targeting the SAFN in providingtherapy. When electrically targeting the PTN, the observation of motorevoked muscle activity in the foot and/or the patient's report ofsensation radiating along the sole of the foot can be used to select andconfirm appropriate target locations for providing therapy. Theanatomical sites for targeting the SAFN and PTN may be confirmedindependently, and stimulation parameters determined separately, oneafter the other, prior to providing therapy. Further, a method fordetermining correct placement of an implanted device may includeassessing candidate locations using percutaneous stimulation. The siteproducing the greatest amount of paresthesia or the lowest threshold ofamplitude at which tingling is detected maybe as suitable site forimplant. In each patient, the optimal site of percutaneous stimulationmay be marked with permanent ink or a tattoo.

Rather than stimulating both the SAFN and PTN, stimulation can occur attwo or more different locations along the SAFN and its branches as ameans of increasing the therapeutic effects. One needle electrode cantarget the SAFN trunk (28 b) while the second needle electrode 28 c cantarget a different area of the SAFN trunk at a location about halfwaybetween the knee and medial malleolus or the anterior SAFN branchlocated cephalad and anterior to the medial malleolus. The second needleelectrode 28 c can also be positioned to stimulate the posterior SAFNbranch (and/or the PTN) at a location cephalad and posterior to themedial malleolus. Alternatively, the second needle can be located abovethe first and can target the infrapatellar branch or other SAFN targetabove, at, or below the level of the knee. The method of FIG. 13A can beused to position the needle electrodes when providing stimulation at twoor more stimulation sites.

As the inventors have described previously (see U.S. Pat. No.9,610,442), due to the different profile (i.e., frequency responsecurves) produced when rat SAFN and PTN nerve targets were stimulated, aswell as the different spinal projections, it may be that the bladderreflex circuits of the SAFN and PTN are at least partially independent.Accordingly, rather than stimulating only the SAFN, additionalimprovement may be obtained when stimulating both the SAFN and PTN aspart of treatment. It is also worthwhile noting that the acute andprolonged responses to bladder stimulation were different and suggestthat individual patients may receive greater benefit when using SAFNrelative to PTN (although potentially the opposite may be true in somepatients), to treat acute urge incontinence symptoms, while greaterprolonged response may be obtained when stimulating the other target.

FIG. 5 shows an embodiment of a neurostimulation system applied to a legof a patient 6 for providing TENS of the SAFN. The neurostimulator 50may be configured to provide stimulation of the SAFN at a first TENSstimulator 30 b at a location on the medial aspect of the leg near theknee, and/or a second TENS stimulator 30 c at a location cephalad andanterior to the medial malleolus, and/or a third TENS stimulator 30 dplaced at a location midway between the locations of stimulators 30 band 30 c (and also which may typically be positioned closer to the tibiato lessen concurrent simulation of calf muscles). A TENS electrode 88can also be placed on the medial aspect of the foot in order to completethe stimulation circuit or pairs of electrodes on the leg may serve toprovide two independent stimulation signals (e.g. between 30 b and 30 d,and between 30 c and 88). Alternatively, the stimulation protocol mayprovide stimulation with a circuit that may only include two electrodeslocated in approximately the shaded medial region of the leg “medialtarget region”. In an embodiment, additional TENS stimulators may beused along the medial aspect of the leg starting approximately at thelevel of the knee in order to stimulate the SAFN. While, electrodes canbe positioned above the knee or on the lateral surface of the leg, butthese may stimulate the sural nerve or other targets rather than theSAFN. This may cause disadvantages in some subjects. For example, ifelectrodes are placed on both the lateral and medial aspect of the leg,the stimulation pain threshold may be lower for the lateral site. Insome people, this may limit the stimulation level that can be providedto the medial target.

The TENS stimulators on the leg 30 b, 30 c, 30 d may be anode, and theTENS electrode on the foot 88 being a cathode (or vice versa), or thisstatus can change with the characteristic of the pulses of thestimulation signal. Only two TENS electrodes on the leg may be used toprovide stimulation. Alternative configurations for TENS electrodes(e.g. bipolar pairs, different sizes of TENS electrodes that change thecurrent density, etc) are well known, have been described in the priorart related to providing TENS stimulation, and can be used with theclaimed system.

In embodiments, any of the TENS electrodes 30 b, 30 c, 30 d, can also beallocated to serve as a patient ground or be used to measure electrodeimpedance or nerve/muscle activity before or during stimulationtreatment (e.g., between stimulation intervals).

SAFN stimulation using TENS with electrodes located at approximatepositions 30 b and 30 d in the figure has been used to provideelectrical stimulation of the SAFN in a study conducted by one of theinventors, where data was collected in healthy individuals who did notsuffer from bladder disorders such as OAB. In 15 out of 15 subjects(100%), we were able to report a cutaneous sensation of tingling(paresthesia) radiating down their lower leg during surface stimulation(Eshani, Hunter, Hassouna, and Yoo, Characterizing the transcutaneouselectrical recruitment of lower leg afferents for the Non-InvasiveTreatment of Overactive Bladder, BMC Urol. 2018 Feb. 13; 18(1):10). Mostparticipants indicated paresthesia down to the level of the medialmalleolus, while some subjects indicated that paresthesia extended totheir hallux. FIG. 6B. shows shaded anatomical plot of the sensationperceived during SAFN stimulation, showing that as the amplitude wasincreased from threshold at which skin receptors were activated (Tskin)to the threshold where discomfort was experienced (Tlimit), the evokedsensation was first felt at the surface electrodes and spread down themedial aspect of the lower leg, past the medial malleolus and evenextending to the hallux, reflecting electrical recruitment of the SAFN(N=15 subjects, note: key=14 since there was not common overlap ofsensation across subjects). These results suggest, for the first time inhumans, that the SAFN trunk could be successfully activated by externalTENS stimulators (which were oriented vertically and positioned mediallyon the lower leg), below stimulation amplitudes that can causediscomfort or pain to the subject. Furthermore, in a subject who did notdetect this sensation at the initial stimulation location, moving theTENS electrode to a second target site and repeating the stimulationprotocol resulted in successful electrical recruitment of the SAFN atstimulation levels below pain. Review of individual data suggested thatwhile sensory recruitment threshold was lower than nerve recruitmentthreshold, and both of these were lower than pain threshold, it was notpossible to predict one threshold from knowing the other (i.e. nerverecruitment threshold could not be easily used to accurately predictpain threshold). These results support that TENS-based SAFN stimulationat targets selected between the knee and cephalad to the medialmalleolus is feasible in human subjects and may serve as an effectivemethod in treating OAB.

Although the maximum amplitude tolerated by participants in this studyranged from approximately 20 mA to 60 mA, other stimulation parameters(such as frequencies between 2 Hz and 50 Hz, or stimulation durationbetween 15 minutes to several hours) may have different maxima and maybe assessed, selected, and then used in patients during therapy, orchanged as therapy progresses. In embodiments, the stimulation waveformscan be a carrier waveform with frequency in the kHz range, such as a5,000 Hz-50,000 Hz (or higher), that is modulated by an activationsignal delivered at 5 to 20 Hz. Additionally, other characteristics suchas amount of body fat, edema, impedance of skin, and conditions such asdiabetes that affects sensitivity to pain may require adjustments in thestimulation waveforms or sites used during therapy for individualsubjects, and may be perceived differently than (or not perceived at allsuch as in the case of some diabetic patients or patients with othermedical problems) the stimulation waveforms used in the above study inhealthy, young subjects. Additional therapeutic benefit may be obtainedby providing the TENS stimulation bilaterally in either a concurrent oralternating manner, with respect to a single treatment session or acrossindividual treatments. Additionally, since the SAFN has been used tosuccessfully produce paresthesia, TENS based stimulation may be used todecrease discomfort associated with foot pain as well as providetreatment in OAB. In an embodiment the maximum amplitude provided by aTENS neurostimulator may range from 100 mA to 200 mA.

Percutaneous TN stimulation therapy treatment sessions typically occurfor about 30 minutes once per week during an induction phase, andapproximately once per month during a maintenance phase. In contrast,during treatment with TENS in a home setting, subjects may provide SAFNstimulation for at least 30 minutes every day, every other day, or atleast once per week during induction. This can occur just as frequentlyor less frequently, for continued benefit during maintenance. Therapymay also include providing TENS during sleep for least one night perweek. Especially during long (e.g. >1 hour) therapy periods, theneurostimulator 50 may realize a stimulation protocol that providesintervals of non-stimulation between the stimulation intervals, forexample, 30 minutes on, then 2 hours off, then 30 minutes on, etc. Thismay provide advantages of both less skin irritation and can also extendperiods between recharging or decrease the size of a battery.

The neurostimulator 50 can be programmed with various “SLEEP” protocolsand features. These can be selected by a patient at bedtime or beprompted or selected automatically by the system as a function ofclock-time. The SLEEP protocol can cause the neurostimulator 50 togradually increase to a selected therapy amplitude across a period of 1hour, and/or delay onset by 1 hour, to decrease the risk of interferingwith a subject's sleep. The protocol may also cause the stimulationamplitude to gradually ramp down after an interval that is defined toend an hour or so prior to when the subject is expected to wake up todeter early awaking. If the system is provided with, or is incommunication with, a sensor (e.g. EEG, EKG, strain, or accelerometersensor), and a processor is provided in a sensing module 55 that is ableto algorithmically assess arousal level, sleep, or sleep stage basedupon sensed data, then TENS stimulation may only occur when evaluationof sensed data meet a selected criterion. For example, stimulation mayonly be provided during certain sleep/arousal stages or only when thesubject is experiencing restful sleep (e.g., leg movement measuresremain below a selected threshold). A stimulation protocol that isdefined for providing stimulation for longer periods (e.g. several hoursat night) can use different stimulation signals than those used during a30-minute therapy session. For example, the amplitude and/or pulseduration of the signals may be lower those used for 30-minute sessions.

Patient Safety Across Stimulation Type.

Stimulation signal amplitudes may be lower when the neurostimulator 50uses needle electrodes rather than TENS electrodes. Accordingly, inorder to provide for patient safety and deter unwanted or unintendedstimulation signals from being erroneously used, a number of hardwareand/or software safeguards can be used. For example, a lead set 24 thatis attached to the device by plug 22 uses a lead set or plug forproviding TENS stimulation that is different than that which is used toprovide percutaneous stimulation, and may even connect differently tothe system. Additionally, these two different types of lead sets/plugscan contain circuitry that adjusts the amplitude of the stimulationsignal output by the device 50 so that it is appropriate to the therapybeing delivered to the patient. The neurostimulator may allow users totoggle the control module 52 to operate in a percutaneous mode or TENSmode. Each mode has a set of one or more stimulation protocol parametersthat create stimulation waveforms that are appropriate for the twodifferent types of stimulators (e.g., voltage, current, pulse-width, orduty cycle). However, for safety or other reasons it may be preferableto use two different lead sets that prevent a user from accidentallyproviding a stimulation signal that is higher or lower than what isintended. The plug 22, can also communicate, or otherwise operate inconjunction with internal modules of the device to adjust the amplitude,or maximum amplitude that is permitted while the plug is attached to thehousing 12. In an additional embodiment two different plug+lead sets canbe used, where the plug that is used during TENS stimulation fits afirst connector of the system and a different shaped plug fits a secondconnector of the system. In an additional embodiment an adaptor can beprovided for a plug that is used during percutaneous needle stimulationthat fits a first connector of the system (and attenuates thestimulation signal by a selected amount) and the plug for the TENS leadset can be attached directly to a connector of the system 10. The leadsets used for percutaneous stimulation may have circuitry thatattenuates the strength (e.g., voltage, current, pulse width) of thestimulation signal output from the device 50, while the TENS lead setdoes not have this additional circuitry. Alternative methods forproviding patient safety are disclosed later in this specification.

FIG. 6A shows an embodiment in which TENS stimulators are applied to theback of a patient to stimulate either lumbar and/or the combination oflumbar and sacral nerves. Current investigations of sacral stimulationtherapy using TENS (e.g. ClinicalTrials.gov Identifier: NCT01940367)instructed subjects to place surface electrodes, 2″×2″ in size, over thesacral foramen S2-4, bilaterally, using 2 channels (4 electrodes total).Approximate locations are over posterior superior iliac spine andinferior lateral angle of sacrum. As is shown in FIG. 6A, using TENSelectrodes more cephalad to the locations used to stimulate sacraltargets 36, such as locations 34 over the lumbar sites L2-L5 can be usedinstead of, or in addition to, the currently evaluated approach toprovide improved therapy. During the provision of therapy, stimulationmay be provided using different patterns. For example, stimulation canbe sequentially applied to contralateral electrode pairs (at the samelevel of the spine) rather than concurrently (e.g. L2 left and L2 right,then L4 left and L4 right), or ipsilaterally (e.g., L2 and L4 left, thenL2 and L4 right), or can be applied to single targets (e.g., L2 leftwith an electrode placed on the patient's thigh to close the circuit).Additionally, in an embodiment, treatment using the lumbar TENS sitescan be used in patients who do not respond to stimulation of othertargets such as at sacral target sites.

Patient Compliance

In a trial, or clinic-based, setting the detection of non-compliance mayallow for corrective measures and interventions that can ultimatelycause therapy to be successful rather than fail. When providingstimulation at home, rather than in a clinic, monitoring and promotingpatient compliance can be essential. Especially in more severe cases ofOAB, an increased amount of stimulation may be needed in order to obtaintherapeutic benefit, rather than 30 minutes once or twice a week.Patient compliance may be a challenge both for TENS, magneticstimulators (e.g. TMS devices) and for ‘implantable’ therapies that arepowered by, or controlled by, external components of theneurostimulation system. In therapy systems that stimulate targets suchas the PTN or SAFN and do not provide for an internal battery inimplanted components, the patient must remember to activate an externalcontroller in order to activate the implanted neurostimulator. Theprovision of a compliance module 200 is important because it is wellknown that patients can be inaccurate about their actual compliance, andthis can be a greater concern for older OAB patients. It may beimportant for a doctor to be able to accurately assess patientcompliance, rather than simply relying on the reported compliance, todetermine if a patient is not responding to therapy due to complianceissues or due to other reasons such as lack of a treatment response in acompliant patient. Accurately tracking compliance may also be importantin assessing efficacy in clinical trials where subjects are expected toprovide self-stimulation outside of a controlled setting.

In embodiments of the current invention the user/physician programmerworks with an implantable neurostimulator. Examples include theStimguard or Bluewind systems which are undergoing clinical trials andanother is eTENS, which we have previously described in application Ser.No. 14/553,427. It is not useful for a doctor to assess compliance ofpatients self-treating themselves at home during a clinic visit, sincepatient compliance reports may not be accurate. Existing TENS systems donot allow a doctor to assess patient compliance outside of their clinicvisits, such as by using remote monitoring. Accordingly, the system 8 isprovided with functional modules that address current limitationsrelated to managing and augmenting patient compliance.

In an embodiment, a compliance module 200 (see FIG. 8) is realizedwithin at least one component of the system 8 such as theneurostimulator 50, and/or the user/physician programmer 70, and/or themanagement computer 71, and performs operations related to patientcompliance. As will be disclosed, the compliance module 200 can operate,and work with the other modules of the neurostimulation system, tomanage, monitor, track, promote, summarize, analyze, display, report,transmit, process, and alert to, aspects of patient compliance. Althoughexisting TENS units can monitor patient usage in the form of totaltreatment time provided (e.g., in total hours) since the reset of acounter, there is no provision for other characteristics related topatient compliance. The compliance module 200 stores a detailedhistorical record of patient use and displays the actual usage,including metrics that reflect usage on a per-hour, per-day, or per-weekbasis. Some additional features and advantages of the compliance module200 of the present invention, that address limitations of theuse-counters of existing TENS devices are now further disclosed.

The compliance module 200 can alert a patient 6 by operating the userinterface module 80 or communication module 68 to provide an alertsignal to a patient about a scheduled therapy interval. The alert signalmay be communicated from a device of the system 8 to a patient'ssmartphone or may be realized as a sonic or visual alert provided by theuser/physician programmer 70. The alerts may be used to alert thepatient (or physician or other intended recipient) to compliancefailures when a compliance criterion is not met. A compliance failuremay occur if a patient fails to provide stimulation for one or morescheduled therapy sessions within a defined time interval (e.g. within24 hours after stimulation was supposed to occur), or in response tofailing to meet other compliance conditions as will be disclosed. Thecompliance module 200 can also alert a user of an upcoming scheduledstimulation session/time.

In embodiments, compliance module functions can be realized, at least inpart, by a customized application operated on a patient's smartphone.For example, an application miming on a processor of a smartphoneaccording to instructions provided on computer readable media can causean alert signal to be issued to a patient or caregiver to notify about ascheduled therapy. In order to promote compliance, the alert can be setto occur prior to a scheduled therapy time (as a prompt), or at aselected time after the therapy if the patient did not provide corrector insufficient therapy (as a reminder), or both.

A smartphone-based compliance application can be considered as onealternative embodiment of the compliance module 200, and may be operatedindependently or in combination with the compliance module 200 of thesystem. A smartphone compliance application that does not communicateand cooperate with the compliance module 200 of the neurostimulator maybe limited and may simply serve as a reminder-system, since while theapplication provides reminders to a patient it may not be able tomonitor and/or determine if therapy is provided by the system 8.However, an integrated system is preferred and wireless communicationbetween the neurostimulator 50 and a patient's smartphone can occur viaradiofrequency, Bluetooth, sonic, infrared, WIFI, or other one-way ortwo-way communication protocol.

FIGS. 7A and 7B show two embodiments of compliance screens that can beprovided using information generated by, stored, and operated upon bythe compliance module 200. FIG. 7A shows a monthly calendar summary viewthat summarizes both total therapy per week (in minutes) as well asmaximum and minimum durations during which individual therapy sessionsoccurred. The weekly summary statistics are presented in the therapysummary table on the left-hand side of the screen and include totalminutes per week, and the minimum and maximum durations for stimulationsessions provided by the system. Also shown in the bottom row of summarystatistics is the integrated time across the entire month, whichprovides a simple patient compliance measure that shows the totaltreatment time in hours.

There may be different compliance criteria that must be met for thepatient to be considered compliant. For example, a monthly therapycompliance criterion may require that at least 2000 minutes of therapybe provided each month. In this example, the patient has met thiscriterion successfully (i.e. the patient provided 2157 minutes).Alternatively, a weekly therapy compliance criterion may includeproviding therapy for at least 120 minutes per week. In this case thepatient did not meet this therapy compliance criterion in the 3^(rd)full week of April where only 60 minutes of therapy were provided. Thecompliance failure is reported by a shaded value of “60”. A therapycriterion can also exist for a time of day, for example a therapycriterion can require a patient to have at least 3 sleep/night sessionsof at least 5 hours each week. Therapy compliance criteria as well ascontingent actions which occur if one or more criteria are not met canbe selected or adjusted by a user, such as a doctor, caretaker, orpatient. A password or other permission schema may be used to restrictaccess to the operations that allow therapy criteria to be adjusted.Additionally, summary statistics can be calculated and displayed by thecompliance module 200 that compare the times and durations a patientprovided therapy in relation to pre-set treatment schedules. Therapycompliance criteria can be set for minimum/maximum durations,stimulation amplitudes to be used during treatment, and othercharacteristics.

FIG. 7B is an alternative view of compliance data monitored, stored,analyzed, summarized and displayed by the compliance module 200 which inthis example is shown in a calculated weekly view that also shows thehours of each day of the week that therapy was provided. This view canbe obtained by a patient (or doctor) by clicking on any week of thecalendar shown in FIG. 7A. Night time data (times when the patient istypically sleeping or as determined by analysis of sensed data such asaccelerometer data) can be shaded in one color (e.g., grey boxes), andtimes when the patient is typically awake can be shaded in a selectedcolor such as white.

Either an implanted neurostimulator or an associated external devicethat provides power/data signals to control therapy can operate acompliance module 200 to generate and log in the device memory a recordof operation. It can further compare information regarding usage tocompliance criteria to monitor, assess, transmit, promote, alert to,generate and store a log related to, and display compliance or lack ofcompliance.

The compliance module 200 can monitor and assess a patient's complianceusing various compliance criteria, such as the following:

A daily compliance criterion can include a minimum amount of time perday during which therapy must be provided, for example, at least 30minutes of approximately continuous stimulation, using a minimumamplitude, on a given day.

A nightly compliance criterion can include a minimum amount of time pernight during which therapy must be provided, for example, at least 6hours on a given night.

A weekly compliance criterion can include a minimum amount of time perweek during which therapy must be provided, for example, at least 20hours per week. Additionally, a weekly compliance criterion can includemeeting the daily compliance criterion for at least a selected number ofdays (such as 3 days per week). A weekly compliance criterion can alsorequire for example, at least 3 days of therapy and further require thata day with no-therapy occurs between each day of therapy. A weeklycompliance criterion may also require that the daily compliancecriterion is met at least twice over the course of a week and thenighttime criterion is met at least once.

A monthly compliance criterion can include a minimum amount of timeduring the month during which therapy must be provided, and may includeadditional compliance criteria such as that at least 2 of the 4 weeksare determined to meet compliance criteria.

Compliance criteria can relate to stimulation protocols rather thannumber of treatments or total therapy duration. For example, acompliance criterion may be managed by a user to adjust the criteria torequire such characteristics as stimulating both legs instead of one legat least once a week. A compliance criterion can require a patient fillout an electronic bladder diary, a quality of life survey, or provideresponses to Likert-type scales that are provided by a device of thesystem 8 according to a schedule such as at least once every two weeks.A compliance criterion can be managed to require that more frequentstimulations such as every other day are provided at the beginning oftherapy and after an interval such as one month, can then be decreasedto require a less frequent schedule of stimulation sessions to beprovided by the user. Compliance criteria can also relate to users whotake medication and can be calculated based upon user input queriesabout whether they have taken their medication. Accordingly, compliancecriteria which include both stimulation and medication criteria can beoperated upon by the system.

In an embodiment, the system 10 is programmed with a stimulation programthat is more frequent in the first days or weeks of therapy. Thisbecomes less frequent only if the patient reports benefit. This can bereported by patient input such as patient responses to survey itemsprovided by the user interface module 80. Additionally, the system mayprompt the patient to answer questions about symptoms (under control ofthe patient survey module 61) and begin to decrement the frequency ofthe treatments after a minimum interval (e.g. 4 weeks) only if thepatient rating data (e.g. selection of a value for a Likert scale) orpatient answers to survey data that are provided in response surveyspresented to the user are operated upon by the system 8 and showimprovement (e.g. QOL scores improve over a selected amount). Thepatient alerting and compliance module 200 parameter values can then beadjusted according to this less frequent therapy. The SAFN may be moresensitive to, and offer an additional mechanism for, stimulationintended to modulate bladder activity. In the unlikely event thatstimulation (e.g., SAFN or combination of SAFN and PTN stimulation)produces an unwanted side effect (e.g., causes or approaches urinaryretention as reflected by patient response to certain survey questionsor analysis of digital bladder diary data), then, in an embodiment, thecompliance module will reduce the stimulation parameters (or prompt theuser to do so) to permit titration of therapy. Adjustment of stimulationparameters may involve adjustment in one or multiple nerve stimulationtargets.

In addition, compliance may relate to enforcement of compliancerestrictions. For example, the compliance module may dictate that apatient cannot provide therapy more than a certain number of timesper-day or other selected interval. The restriction can be assessed bycomparing usage to interval rules that can limit stimulation for aselected interval. Further the restriction can be defined as acombination of time, number of stimulations, and treatment strengthwhich is accomplished using an interval rule type referred to as aninterval-strength rule. For example, a patient who uses largerstimulation amplitudes may be restricted to a lower number of maximumtreatments within a selected time interval. In an embodiment, a sum oftreatment times can be weighted by the stimulation strength. Unlikemedication, where a patient ingests a certain number of pills over thecourse of a defined interval and must obtain refills at the end of theinterval, there may be no evidence of patient over or under usage ofelectrical therapy in the absence of the compliance module 200.Accordingly, without a compliance module, detecting and deterring theoccurrence of either over or under stimulation is difficult toaccomplish.

The compliance module 200 allows doctors or patients to adjust howcompliance is managed by selecting what the compliance criteria are foran individual as well as how and when the therapy schedule may changeover time. Both usage and compliance can be tracked over time, and thiscan be displayed to a user or remotely to a doctor. The promotion ofcompliance can occur with setting reminder alerts to occur before ascheduled stimulation session, or after the time when this was scheduledif it did not occur, etc. Reports related to usage and compliance can bestored and transmitted over computer networks to allow for remotepatient monitoring and management. The various features should improvepatient compliance.

In the case of patient non-compliance various operations may occuraccording to the compliance module 200 in conjunction with the othersystem components and methods of the invention. For example, failure tomeet a monthly compliance criterion for X out of Y months, or for aselected number of sequential months, can result in the compliancemodule 200 causing an alerting module 204 to cause a signal to beprovided to the patient or medical care provider. Alternatively, acompliance module 200 algorithm may cause the neurostimulator todeny/restrict stimulation until it receives a reset signal from a remotephysician computer 70′. Additionally, the patient prescription statusflag may be changed to inactive in the remote physician computer 70′. Inother words, if a patient is not compliant and then wishes to use aneurostimulator then they may first have to meet with their doctor todiscuss the non-compliance and have their device re-enabled. The doctormay need to submit the compliance record of the patient and evidence ofa patient visit in order to obtain an approval from an insurance carrierto re-activate a neurostimulator of a patient. This may further be tiedto requiring a new prescription be written and prescription statusupdated in the system.

The compliance module may operate to provide different alerting schemesfor treatment of different disorders. For example, if the TENS system isused for providing transcranial direct or alternating stimulation (i.e.tDCS or tACS) in the treatment of depression or anxiety, failure toadhere to a treatment schedule may result in the system communicatingwith a computer 70,70′ to alert a doctor or caregiver that a patient isnot complying with a therapy regimen. Alternatively, if the tDCS/tACS isused to provide cognitive enhancement, then no such notification mayoccur. In an embodiment, compliance operations rely upon timingcircuity, such as a real-time clock, to calculate times and datesrelated to when and for how long stimulation was provided.

In an embodiment, the compliance module 200 is configured to generatereports based upon processing of compliance data to generate compliancesummary data and usage date to generate usage statistics. The reportsmay be transmitted to a clinic or remote computer 71 or are generated bythe remote computer using compliance or usage data. The system 8generates reports according to a schedule or due to doctor request ordue to periodic processing of the compliance data and detection ofnon-compliance. Non compliance can be detected when the compliancesummary data are compared to, and fail to meet compliance criteria. Thecompliance statistics over time are displayed as trend graphs whichallow the tracking of compliance and show periods and rates ofcompliance as therapy progresses. When presented as summary statisticsthe compliance may be reported for the last week, month, and sincebeginning of treatment (e.g. 100% compliant for the last week, 90% forthe last month, and 95% since the beginning of therapy). A report ofusage can include such statistics as number of weeks since start oftherapy, total stimulation sessions, average number of stimulationsessions scheduled or provided each week, average length of stimulationsessions, average strength of stimulation sessions. A table can also begenerated where the date, time, duration, and stimulation settings foreach session are listed. When trend data is presented for patient inputdata such as urge scores, this may be presented separately for day andnight as defined by user (e.g, day 8 a.m. to 9 p.m and night 9 p.m. to 8am). When a user first operates the device 50 it may present the userwith a set of treatment customization items that allow the user toadjust the schedules for providing patient input or treatment. Forexample, how many times a week survey questions should be asked as wellas what time these should occur.

The payments and permissions module 202 can communicate with a remotemanagement (e.g., a computer of an insurance company) or physiciancomputer 70,70′ to ensure that a patient is in good standing beforeenabling the provision of therapy. For example, a remote management orphysician computer may assess whether 1. The patient has met variouscompliance criteria; 2. The patient has an active prescription for thetherapy from their doctor which has an associated “active” status flagthat is set in the neurostimulator; 3. Insurance is in good standing; 4.The account associated with the neurostimulator has not been flagged forany reason, such as a) doctor has failed to meet with the patient fortoo long a time since prior visit b) the neurostimulator is scheduledfor calibration/maintenance/replacement or c) the neurostimulator hassent flags related to device operation, faults, failure to meetcalibration and/or self-test routines etc.

FIG. 8 shows a neurostimulator device 50 that can be used to realize themethods and systems of the current invention. The neurostimulator 50 isillustrated with modules and components which may be included, omitted,or modified in various embodiments. The modules provide functionality tothe neurostimulator and, while shown discretely, may share software andhardware components with each other. Further, each of the modules may berealized within the neurostimulator housing, outside of the housing, orboth (i.e. in a distributed manner). Modules may be realized jointlybetween the neurostimulator 50 and an external device such as auser/physician programmer 70 and can be redundantly provided withindifferent components of the neurostimulation system. For example, analerting module 204 may be realized within an implantableneurostimulator, an external neurostimulator, a user/physicianprogrammer, and/or a remote management computer (or a computer networkof which it is a part).

The device 50 comprises a control module 52 with circuitry forcontrolling the various other modules of a neurostimulation system 8.For example, under its direction, the stimulation module 54 and sensingmodule 55 can be controlled according to user input commands and/ortreatment protocols and parameters stored in the protocols andparameters module 66. Treatment protocols can include stimulationprotocols, sensing protocols, alerting protocols and evaluationprotocols. A non-transitory computer-readable medium is provided in thecontrol module that is configured for storing one or more instructionsconfigured to be executed as part of a treatment protocol by at leastone processor of the system, which can be at least one processor of anelectrical stimulation device 50 or a user/physician controller 70, or aremote physician computer 70′ that communicates over theinternet/intranet with rest of the system. These protocols may enablethe control module 52 of the device 50 to responsively adjust itsoperation in relation to, for example, the evaluation of sensed data(e.g. accelerometer data) or detection of defined events as provided bythe sensing module 55, patient input data managed by the user interfacemodule 80, time intervals assessed by the control module 52, and othertriggers that can cause the selection, provision, and adjustment oftherapy as defined by the parameter values and algorithms related to aparticular treatment protocol. The device 50 can also simply providestimulation in response to user input when operated by a user.

The control module 52 has a timing module 56 including a real-time clockand a timer, a processing module 58 including at least one processor foroperating software, and processing information and parameter settingsthat are stored in memory module 60 and which allow for control ofdevice 50 operation. The real-time clock can be used to calculate datesand time to provide event logging and to provide operations related tothe compliance module 200. The current date and time can be compared tothe date and time of the last stimulation that was provided and thepatient can be alerted if a selected amount of time has passedindicating that a treatment is due or has been missed. The time and datecan also be used to define and/or realize interval rules whichdetermine, for example, the minimum interval that must occur betweensubsequent stimulation periods. The date and time can also be used bythe payments and permission module 202 to determine if the device isstill operating within an interval allowed in relation to payment. Thestimulation module 54 can control at least one waveform generator/signalprocessor such as simulation module 62 that contains circuitry forgenerating pulses or arbitrary waveforms for output includingalternating current (AC) and/or direct current (DC) signals to be usedby one or more electrical, magnetic, optical, sonic, ultrasonic or othertypes of stimulus transducers.

The sensing module 55, may be realized as part of the AD/DA module 64when AD/DA circuitry (including AC-to-DC, DC-to-AC, and DC-to-DCconverters, and allows for both signal generation and acquisition. Thesensing module 55 contains circuitry and protocols for conditioning andanalyzing sensed data and can also for providing power to, and/orcommunicating with, various sensors including, for example, position,acceleration, electrical, electromyographic (EMG), electroneurographic,pressure, optical, sonic, and other sensors that may be used by thesystem. The processing module 58 enables the assessment of sensed dataand can provide detection of events that are defined to cause deliveryor adjustment of stimulation. Responsive stimulation may occur in aclosed loop manner, via rules or control laws, or may cause information(information about the sensed data) or signals (a flashing light) to bepresented to a user of the device 50, such as by an external patientdevice 72 or physician programmer 70, to prompt provision or adjustmentof therapy. The processing module 58 may be configured to store data inmemory 60 such as historical sensed data records to track patient data,or assessment of sensed data along with usage and compliance data.

An AD/DA module 64 allows for conversion of input and output signals aswell as amplification, digital signal processing, filtering,conditioning, and also contains safety and regulation circuitry toensure patient and device safety. The AD/DA module 64 may also containcircuitry for multiplexing signals across different sensors orstimulators, and can contain switches and controllers for routing andcontrolling electronics of the system.

The apparatus 50 also includes a communication module 68 for providingwired and/or wireless communication with other system components (e.g.RFID identification to communicate between system components) such as auser/physician programmer 70 or management computer 71. Thecommunication module 68 can communicate with a computer at remotemedical facility 70′ (to allow data communication and programming tooccur remotely) either directly or by way of the user/physicianprogrammer 70. The communication module 68 can provide signals totransceivers which provide one-way or two-way communication of wirelesspower and/or data signals to implantable components such asneurostimulators. All wired or wireless communication can be realized atleast partially using the internet, or a local area network.Communication may also include means for magnetic, radiofrequency (RF),optical, sonic, and/or other modes of data and power communication withother devices. The communication module 68 may include circuitry,hardware, and protocols for providing WiFi, Bluetooth, cellular,magnetic, magnetic inductance, microwave, RF, electrical, optical,sonic, RFID, or other types of communication usingcommunication/interface ports 82, 144. For example, the ports 82, 144may connect to a system component which provides for wirelesscommunication of data or power signals.

The communication module 68 is configured for use with USB connectors(e.g. 83 c) and the like which may be provided as part of a userinterface panel 82. The communication module 68 of the device 50, aswell as communication circuitry may operate to send or receive signalsusing near field, far field, induction, magnetic resonant inductioncomponents, coils (e.g. an inductive coil assembly for powering animplantable device), antennae, and/or rectennae, optical sensors andstimulators, sonic stimulators and sensors, etc. This allows forsuccessful communication of identification, data or power signalsbetween any external and internal components of a particular embodimentof the invention. The apparatus 50 also has a power supply/rechargemodule 74 which can include components such as a battery, AC and DCconverters, diodes that function to rectify wireless power signalsharnessed by rectennae and circuitry related to the conversion orprovision of power which may be related to harvesting or transmission ofwireless signals, and can include a power cord for connecting to a wiredpower source through at least one of the communication/interface portsof panel 82.

The interface ports 83 may be connected to communicate with and/or powervarious sensors, such as sensors that are configured to measure bladderactivity, bladder pressure, bladder fullness, foot twitch, or othercharacteristic related to a condition or disorder being treated. In anembodiment, urodynamic measurements can be assessed before and afterstimulation to determine the effectiveness of a given set of stimulationparameters.

A signal routing module 63 provides components and switches that operateto route signals between components and modules of at least oneneurostimulator 50. For example, when a TENS protocol is selected themodule 63 may route the stimulation signals to a first connector 22 onthe housing of the device 50, while when a percutaneous signal is usedthen this is routed to a second connector of the device 50. Signalrouting may also be used when two or more stimulation targets arestimulated to route the signals to the appropriate set of needleelectrodes or TENS stimulators. Signal routing may also be used to sendsignals to a subset of TENS electrodes.

The I/O interface module 75 can contain circuitry and protocols forrouting signals and controlling communication related to various inputand output ports such as USB or other ports and can further containsafety circuitry and regulators that protect the patient and device 50from other devices that may be connected to the neurostimulator 50.

The communication module 68 can cooperate with the user interface module80 which contains hardware and software for presenting information to auser (e.g. patient or physician) and obtaining information/input fromthe user. Although the device 50 may communicate with a physician orpatient programmer 70, or external patient device 72, such as may berealized by a specialized device, smartphone, tablet computer orwearable device, the device 50 may also have at least one signalingmodule 78 (which can be part of the alerting module 204) with relatedcircuitry and control a display 79 for presenting visual data in bothtext and graphical format. This may also be used to present a user withvisual alarms related to the provision of therapy and/or to operate aspeaker 38 for presenting auditory signals such as instructions topatients related to the therapy (e.g., an instruction may inform apatient that a TENS pad may need to be re-applied or replaced becausethe impedance value is too high). The signaling module 78 can have aBluetooth enabled sound system that communicates with a speaker 38, orsound transducer such as a hearing aid by way of the communicationmodule 68. The device 50 can also contain patient interface module 80that permits operation of, and includes, controls such as a keyboard,microphone, nobs, switches, etc. to allow a user to provide input. Inputcan be confirmed, for example, by an “enter” button 19. The interfacemodule may also provide for a menu guided system that allows foradjustment of device operation. It is obvious that various modules suchas modules 78, 79, and 80 can also be realized within the physician orpatient programmer 70,70′.

In an embodiment, the device 50 or user interface module 80 isconfigured with an algorithm that operates according to rules or anartificial intelligence (AI) program that is operated upon by theprocessor 58 that collaborates with the user interface module 80 toverbally instruct the user on how to set-up, adjust, and use thestimulator. For example, the system instructs a user to put the deviceon their leg and then delays further instruction until the expiration ofan interval or until the impedance circuit indicates the device 50 isacceptably connected to the patient's skin. If the impedance value isnot acceptable then the device provides additional instructions to theuser. The device also is programmed with an option to communicate with avoice service (e.g., Alexa) to allow interaction with the user via voiceprompts as well as sensors on the device 50 such as impedance andaccelerometer sensors. The AI program of the interface module 80 isfurther configured with algorithms to assist with determining treatmentcharacteristics such as selecting stimulation parameters that aresuitable and comfortable for the user, and also providing instructionsand answers in response to questions posed by the user.

In an embodiment, the system 8 incorporate or is adapted for use byelectrostimulation devices, designed to treat symptoms of diseases anddisorders such as incontinence by stimulating muscles (and/or nerves) inthe pelvic area. For example, muscle stimulators serve to provideexercise and feedback to the receptors and muscles of pelvic area ofusers suffering from incontinence. In embodiments, the system is alsoadapted to control or communicate with devices that stimulate thepudendal nerve to contract the external urethral sphincter muscles, orother devices that serve to provide stimulation inside or outside of thebody to stimulate muscles to assist with symptoms such as incontinence.

Both the control module 52 and the waveform generator module 62 may beconfigured with safety hardware and software routines, and can operatein combination with calibration routines of a calibration module 61 tocalibrate the apparatus 50 and to ensure proper functioning Inembodiments, the control module 52 allows stimulation programs to beimplemented according to protocols stored in the device memory andaccording parameters that can be adjusted by a user's manual inputobtained by the patient interface module 80. The safety routines of thesafety module 208 may limit the adjustments made by a user to rangesthat are safe.

The interface port panel 82 allows for connection to various systemcomponents. The device 50 may use at least a first stimulator conduit84, a second stimulator conduit 86, to communicate signals to a firststimulator 28 b and second stimulator 88. Conduits can comprise singleor multi-stranded electrically conductive, insulated electrode leadwires. The first conduit 84 has a first end connector that may contain aplug that electrically couples to a first stimulator interface port 83 aof the interface 82. When the device 50 is used to provide stimulationusing non-TENS modalities the third stimulator interface port 83 c maybe configured to be connected to a TMS device to control the provisionof magnetic stimulation as part of the system and method of the currentinvention.

Alternatively, the wired interface port 83 c can allow for connection tosensor components. When the stimulators are TENS electrodes, then thesecan serve as both stimulator and sensor, typically at different momentsin time. Stimulation electrode 88 can serve as sensor when the sensingmodule (or impedance module) rather than stimulation module isoperationally connected to a specific port during a selected period.However, other types of sensors may also be used.

In an embodiment, the interface port panel 82 may only consist of one ortwo connections that are distributed on the device housing. For example,the neurostimulator 50 can be realized in the form factor shown byneurostimulator 51 a and utilizes a transcutaneous electrode pad such asthose commonly used to provide TENS, which may have bottom surface thatis an adhesive and conductive surface (for attachment to a patient) anda top surface configured with connector 89 a which may be realized as anadaptor such as a metallic snap to be connected and disconnected to aconnector either on the bottom surface of the housing of theneurostimulator 51 a, or to connect to the end of a lead set. Theneurostimulator 51 a may have a lead set 86 containing a single leadwire for electrically connecting a single needle electrode 28 b or TENSelectrode 88, to the neurostimulator via connector 22. Alternatively,the lead set 86 can contain multiple lead wires for electricallyconnecting one or two percutaneous needle electrodes, and a TENS pad tothe neurostimulator via connector 22.

The alerting module 204 provides functions related to patient alertingand can include providing alerts using sounds emitted by a speaker 38 orvisual alert signals provided by displays 79 or communication signalssent using the communication module 68.

The impedance module 206 operates to promote impedances of the leadsused during stimulation are below an acceptable threshold level such asby providing a user with an alert if the impedance data is above thislevel. This is important for home users because stimulation will not beeffective if the TENS pads do not have good contact with the patient'sskin. Patients may not be well trained to notice incorrect placement ofTENS electrode or the occurrence of bad skin contact.

The patient safety module 208 can provide operations and controlhardware related to ensuring patient safety. For example, if the moduleassesses that a calibration or maintenance date stored in the module haspassed it may set a flag and provide a message to a user or may notallow device operation until the flag is reset when the indicatedoperation is provided. The safety module may also not permit certainoperations such as providing patient treatment when the device 50 isconnected to a recharging power source.

Payments and Permissions

The payments and permissions module 202 provides for management ofdevice operation. This can include setting what operations and valuesare permitted to be accessed by a user. Passwords orbiological/biometric markers (e.g., EKG or face recognition) may berequired to grant access. The module 202 can also allow a user toprovide information related to using and purchasing of treatmentcredits. In an embodiment this includes medical billing information,reimbursement codes, credit card account numbers, user or clinicinformation, and other information related to payments or treatmentcredits. For example, submission of current procedural terminology (CPT)codes can allow for appropriate coding of the service with diagnosisusing ICD-9 code as determined by the Centers for Medicare and MedicaidServices (CMS). These relate to determination of associated fees forproviding stimulation. The reimbursement codes are based upon treatmentcharacteristic such as if SAFN or PTN targets are being stimulated, andif the stimulation protocol being used is for one leg or for both legs.Reimbursement codes used by the system 10 may be country or regionspecific. Additionally, the payments and permissions can be modifiedaccording to region or state. For example, certain states may covercosts related to certain types of stimulation protocols while otherstates may not and so the operation provided by the system 10 or thetype or amount of a charge associated with a particular treatment creditmay be adjusted accordingly. Information related to a patient or apatient's insurance may also be used in the processing of the treatmentcredit information. This can allow the cost for severe or moderatepatients, who may need more stimulation sessions, to pay the same amountas patients who need less.

In an embodiment, a neurostimulator 51 a is preferably configured tocommunicate with a computer system 71 which provides a treatment creditpurchasing system and also allows for monitoring the status and usage ofa neurostimulator. For example, the neurostimulator 51 a can communicatewith the computer system wirelessly or through an input/output connector144 a which may be realized as a USB connector. Information can also beprovided to the neurostimulator 51 a using a portable digital storagedevice such as a USB flash drive. The USB flash drive may allow two waydata exchange between the computer system and the neurostimulator or mayonly be used to update information in the neurostimulator.

If wireless communication is not available near a user of aneurostimulator, a user is not technically savvy, or if there are otherreasons (e.g. regulatory) why a neurostimulator may not be provided withwireless connectivity, it may be advantageous to provide a physical key,such as a USB memory key. In an embodiment, the key is programmed to beread by the neurostimulator and to provide a selected number oftreatment credits, or to allow the neurostimulator to operate for aselected amount of time or until a specific date. The USB memory key mayfit into an I/O port 144 of the neurostimulator, which can then read theUSB key and update its internal parameters. In an embodiment the USB keymay be required to be attached to the neurostimulator during use. TheUSB key and the neurostimulator may be matched 1-to-1, via the paymentsand permission module 202 which may be programmed to only read a USB keyhaving a particular ID code: the USB key can only be used with aparticular neurostimulator. A patient can receive a USB key in the mailand can mail back a previously sent USB key. Alternatively, a patientcan be mailed a code that can be manually input by a patient tore-activate the neurostimulator for a duration or to provide additionaltreatment credits, according to a prescription or otherwise.Alternatively, a smartphone running specialized application software cancommunicate with a remote computer 71 and the neurostimulator 51 a tomanage treatment credits. This allows the neurostimulator to remainrelatively simple, and the circuitry and hardware of the smartphone maybe relied upon.

In embodiments the neurostimulator 51 a includes a control system 52with a microcontroller/processor 58 which operates the payments andpermission module 202 to manage and store information relating topayment credit status, historical usage, compliance data, and otherparameter values of the neurostimulator 51 a. The payment status andusage information may be transferred between the neurostimulator 51 aand the computer system 71 when the neurostimulator is in communicationwith the computer system 71. The control system 52 monitors the value ofa treatment credit counter which indicates a treatment credit valueassociated with the number of treatment credits that are available.

A treatment credit can correspond to allowing for various types oftherapy provision. For example, a treatment credit can be set equal to atreatment session of, for example, 30 minutes of continuous stimulation,and after a treatment session is completed, the number of availabletreatment credits is decreased by 1. Further, a therapy session may haveto be interrupted or paused. Accordingly, in an embodiment a treatmentsession can have a minimum duration defined before a treatment credit isused, such as 15 minutes. The treatment sessions can also be defined asa selected interval of total provided stimulation (e.g. 30 minutes). Theinterval may be allowed to occur within a selected interval (2 hours).This can allow for 1 or more interruptions or pauses to occur duringtreatment. If there are no more treatment credits available to theneurostimulator 51 a, then the processor 58 operates in a manner thatprevents the neurostimulator 51 a from providing a session of treatment.For example, this can be done by preventing operation of the stimulationmodule 54 and also presenting a user with a message or alert using thealerting module 204. In this case, additional treatment credits can bepurchased and uploaded into the neurostimulator 51 a to allow forsubsequent treatment sessions to occur.

In an embodiment the compliance module 200 works with the payment andpermission module 202 to realize gamification of therapy. For example,if a patient is compliant by providing patient input about theirsymptoms or providing therapy in response to a defined treatmentschedule then a treatment point value is increased. and if they are notcompliant according to one or more defined compliance rules, then atreatment point value is decreased. Treatment points can be defined tocontribute to different treatment point categories, such as compliance,length of treatment, rate of entering patient input data. For example,if a patient typically provides self-stimulation within 1 hour of theirscheduled time then that could be 2 points. If the treatment occurs onthe right day, but many hours after the scheduled time, then they canget 1 point. If they skip the treatment 1 point is subtracted, and ifthey skip 2 sequential treatments 2 points are subtracted. Points canalso be given for answering questions, such as those prompted by thedevice in the morning which questions the user about nighttime voids orleaks. The set of treatment points are calculated upon to generateratings or user status levels such as “Excellent patient”, “Very goodpatient”, “Good patient”, “Late Patient”, “Uncooperative Patient”, etcor are used to calculate one or more scores. The treatment points can beassessed over an interval such as a day, week, or month. As withgamification schemes, selected scores can result in winning prizes orawards which may be purely symbolic. Alternatively, prizes or awards forcertain treatment point categories can be used to further incentivizepatients with economic incentive. For example, points can result in“winning” a free treatment credit or a discount code which can be usedto order supplies such as replacement TENS electrodes. The treatmentgame rewards may be managed by the payment and permission module 202, orotherwise. In an embodiment, the discount is applied automatically to ashopping cart feature of module 364 of the software application operatedin the user device.

If the neurostimulator 51 a is not used during an interval defined fortreatment, or is used less than a minimum selected amount (e.g. 15minutes) then the payment and permission module 202 of theneurostimulator 51 a can automatically increase the stimulation-creditvalue by 1 to the prior value. When multiple patients are treated by theneurostimulator, the physician can enter the patient ID into either aphysician computer or the neurostimulator so that a particular patientis associated with the stimulation session.

In an embodiment, the neurostimulator is permitted to providestimulation therapy-sessions while the treatment credit value is zero ornegative, as long as the stimulation credit value of the neurostimulatoris above a defined payment threshold such as −50 units. Further, atreatment credit rule can be implemented by the payments and permissionsmodule 202 of the neurostimulator 51 a, whereby the negative valuereflecting a treatment credit deficit must have lasted less than aselected interval such as 90 days. This feature can be important forsome clinical practices since a clinic may not be paid or reimbursed fora treatment session until several weeks or months after a treatment isprovided to a patient. In this manner, a clinic does not have to pay inadvance for credits that may not be used for some indeterminate time inthe future.

For various disorders or treatment regimens, a session-based stimulationparadigm may not provide an appropriate unit of therapy. For somepatients and disorders more than one session will occur during aparticular day. For example, when the neurostimulator 51 a is used forproviding treatment related to pain, migraine, headache, sleep apnea,etc., rather than for treatment of overactive bladder, then severaltreatment sessions can be needed to relieve symptoms. The patient and/orclinic should not be required to use multiple treatment credits. If atreatment credit allows providing only a single session then problemswill occur in some patients worry about cost. Certain patients will useless treatment credits rather than providing themselves with additionalneeded therapy.

In embodiments each treatment credit enables stimulation therapy to beprovided multiple times across a selected interval such as a single day,week, or other defined period. Further, the neurostimulator payment andpermission module 202 is configured so that a maximum number (e.g., 10)of treatment credits can be delivered to a neurostimulator 51 a at aparticular time. This provides for an advantage that a patient mustcontact a doctor or service provider after a period of, for example, twomonths. Further, although at least one treatment credit is available,the payment and permission module 202 of the neurostimulator 51 a maynot allow therapy to be provided in selected circumstances. This mayoccur if a compliance criterion is not met or, for reasons related topatient safety, a certain number of stimulation sessions, or totalstimulation time, may only be allowed to occur within a selectedinterval such as 1 day.

In an embodiment, the user notification module 360 providesnotifications to a user or remote medical personnel using light andsound transducers of the neurostimulator 52 a or user/physicianprogrammer 70, or other system component. It communicates with acomputer at a remote location 71 such as a doctor computer using wiredor wireless communication

The web-meeting medical assistance module 362 provides softwareapplication, and multimedia hardware (e.g. video camera and microphoneof a smartphone miming the treatment application software of the system)which support virtual online meeting capability and also permits amedical professional to view the treatment log of a user to assesstreatment history.

The digital shopping cart module 364, allows for in-app purchases usinga digital shopping cart and allows for purchasing of treatment credits,subscription fees, ordering of replacement stimulation pads or otherpayments associated with use of the system. This module also allows forthe provision of discount codes and rebates to be applied againstpayment as may be obtained due to a user achieving selected treatmentgoals monitored by the compliance or gamification modules.

The video and multimedia module 366 provides users with videos that canbe relate to providing the neurostimulation treatment correctly 368.

The gamification module 370 allows for points to be allocated to usersscores as a function of compliance or non-compliance or in return forthe user performing operations that are conducive to obtaining therapybenefit such as providing longer stimulation sessions than are necessaryor watching vidoes related to positive lifestyle changes they can maketo decrease unwanted symptoms of a disorder.

FIG. 9 shows a block diagram of circuitry modules provided in anembodiment of the neurostimulator 51 a. A graphic display 20 such as anLCD visually presents information related to operation such asneurostimulation parameter values or information about compliance asshown in FIGS. 7A,7B, power levels, elapsed time of stimulation, andtreatment credit information. Patient input control can be realizedusing buttons such as power button 14, dedicated buttons 16 (e.g.,start/pause/assess button), navigation controls 18 to assist a user incontrolling the operation of device 51 a via theprocessor/microcontroller 58 of the control module 52. The “assess”button allows the assessment of different stimulation parameters such asamplitude prior to providing therapy. The processor 58 controlsoperation the stimulation module 54 which includes a high voltage supply(DC to DC converter 154), pulse generating circuitry 140 and presentsvalues of related operational characteristics on the display 20 usingcontrol circuitry of the control module 52 including a set ofcontrollers 148. The pulse generating circuitry 140 can also providecircuitry that cooperates with the lead set to blow a fuse after theprovision of simulation as is done in commercial systems that utilizesingle use paradigms. The controllers 148 can act as sets of one or moreswitches or be otherwise realized to adjust and control the operation ofcomponents of the stimulation module 54 including, for example, a DC toDC converter module 154 (or realized as any other signal conditioningmodule), digital-to-analog/analog-to-digital converters 152 undercontrol of the DA/AD circuitry module 64. The controllers 148 can alsoact as sets of one or more switches or be otherwise realized to adjustand control the operation of the sensing module 56 to provide sensing atone or more sensors. The stimulation module also communicates with thewireless module 210 to provide power and/or data wirelessly tocomponents of the system 8, such as an implantable neurostimulator ordirectly to human target tissue as may occur in TMS treatment fordisorders such as depression, migraine or headache. One or more alertingcomponents 156 may include a vibrating buzzer, speaker, light emittingdiodes, etc. may be provided for notifying a user or patient aboutinformation relevant to therapy. This can include an indication, forexample, that a treatment session is completed or is scheduled to occur,an impedance value is above a selected amount, a time has elapsed, thepower has fallen below a selected amount, or other problem has occurredwith the neurostimulator 51 a.

In an embodiment, at least one port 144 enables communication to occurby way of the communication module 68 between the device and othercomponents of the neurostimulation system 10 such as a USB, micro USB,or conductive cable connects to an I/O interface 168 module that canhave isolation electronics such as an isolator 158 and isolated DC-to-DCconverter 160 in order to electrically isolate at least one of the I/Oports 144 a,144 b from the other circuitry and components of theneurostimulation system 8. The neurostimulator 51 a can also include apower management/charging module 74 with a power management circuitry toregulate power operations. The power management/charging module 74 caninclude, and be disposed between, a battery 142 and the processor 58.The power management module 74 can have components to charge the battery142, such as a wireless power harvester (e.g. induction coil configuredfor receiving energy by magnetic induction or rectennae configured forreceiving RF or microwave energy) and associated circuitry, and/or canbe configured for recharging the battery 142, using power from an I/Oport 144 b. One or more fuses can provide for both patient and devicesafety, such as fuse 164 disposed between the battery 142 and processor58, or battery 142 and the other components of the powermanagement/charging module 74. Regulators can be provided such asregulator 166 for maintaining a constant supply voltage to the I/Ointerface 168 when I/O ports 144 a and/or 144 b are connected toexternal equipment. Although shown as portable devices, theneurostimulators shown herein may be configured to be recharged usingpower converter that is plugged into a wall socket, with appropriatesafety.

FIG. 10A, shows a menu screen of a computer system such as a computer ina medical clinic that is connected to the internet. In an embodimentrelated to use of neurostimulators 51 a in a clinic, the computer mayserve as a user/physician programmer 70. The menu screen 170 is a userinterface and includes virtual buttons that allow selection ofoperations related to managing one or more neurostimulators 51 a. Eachvirtual button of the menu screen 170 can be supported by acorresponding module which includes all software and hardware requiredfor implementing related tasks. For example, the manage treatmentcredits button 172 a is part of a module that allows for purchasingtreatment credits to be used with a particular neurostimulator 51 a, andcan operate with the payments and permissions module 202 of the system.

The user of the menu screen 170 may be a patient, doctor, technician,health care professional, office employee (with sufficient permissions),or anyone that manages treatment sessions with patients. The menu screenserves as a user interface that allows for user input and may beconfigured differently for different users. Pop-up dialogue boxes withfields for user ID and passwords can be presented to a user for makingcertain selections or adjustments. Clinic staff can enter ID codesassigned to the clinic to modify, view, and selectively adjust valuesrelated to a patient account, including managing payment credits,patient customer's account and related to programing and/or settingoperating parameters of a neurostimulator 51 a. The menu screen 170 isaccessible from web-based application using a physician programmer 70 orcomputer.

A screen component shows status settings 174 related to one or moredevices being adjusted by a user operating the menu, including deviceidentification and use/connection status.

A button control, and associated module, is shown for managing treatmentcredits 172 a. This selection invokes additional screens for managingand purchasing treatment credits, requesting treatment credit refunds,and for viewing a history of treatment credit transactions. It can alsoinclude dates and times of treatment credit purchase, download, therapyprovision, patient ID and reimbursement code information, and otherinformation. In an embodiment, a treatment credit can contain datafields having information about characteristics of the therapy to beprovided such as the maximum treatment session duration, or can containan interval or date during which the stimulation may be provided.Treatment credits may be provided with an expiration date after whichthey can no longer be used and become “expired”. These may be exchangedfor new treatment credits or “refreshed” using the module.

A button control, and associated module, is shown forrefreshing/restoring 172 b which will update the values on the statusscreen 174 to reflect for example, the current number of treatmentcredits for one or more neurostimulators 51 a. The selection can alsoprovide screens with options to, for example, restore a device to itsdefault values, clear device memory, etc.

Additional selections that are provided include a button control, andassociated modules, for adjusting account information related to aclinic or patient 172 c.

Additional selections that are provided include a button control, andassociated modules, for providing technical support such as viewingmanuals or instructions on how to operate the device, or providing achat window with a customer service representative 172 d.

An additional selection that is provided is a button control, andassociated module, for performing a calibration or diagnostic routineand displaying the results including whether the device passed varioustests 172 e. The selection can allow for running diagnostics such as adiagnostic check on a device 51 b using a USB or other cable (loop-backcable), or by sending instructions and receiving data related tocalibration and system test results wirelessly and if necessaryrequesting technical support 172 d.

An additional selection that is provided is a button control, andassociated module, for managing or requesting reimbursement fortreatment by a patient's insurance company 172 f.

An additional selection that is provided is a button control, andassociated module, for viewing usage and compliance 172 g. This permitsobtaining, viewing, and managing historical data records related tousage, and further presented in relation to compliance criteria. Menuscreens invoked when this button is selected can provide for a graphicalor table view of the usage of one or more neurostimulators 51 b. Thiscan include information on patient ID, number and ID of associatedtreatment credits and reimbursement codes and payment informationassociated with the credits. This can include screens of patient usageas shown in FIGS. 7a and 7b . This can also include screens that allowfor programming of compliance criteria such as weekly treatment goals aswell as what to do in the case that criteria are met or fail to be met.Options related to how, when, and what information is queried of thepatient (e.g., about symptoms, medication compliance), and schedulingpresentation of survey items is also provided.

A button control, and associated module, is shown for allowing a user toadjust or run a treatment session 172 h using an invoked menu interfaceto select or adjust a stimulation program and control theneurostimulator 51 a to provide treatment. The treatment module 172 hand control module of the neurostimulator may both containnon-transitory machine-readable storage media configured to storemachine-executable instructions that is executed by processors of thesystem and can also include, for example, a look-up table, formulas,algorithms, a database having a matrix of treatment protocols and valuesassociated with the protocols. For example, each column associated witha particular treatment contains parameter value settings such asfrequency, amplitude, duration, duration of therapy, stimulator at whichthe signal is applied, inter-therapy intervals during which stimulationis not provided, number of maximum treatments allowed per day, number oftotal time allowed per day, maximum stimulation strength allowed, andany other operational parameter related to treatment withneurostimulator that is external, percutaneous, or implanted.

An additional selection is an “Administrative” button control 172 i, andassociated module, for providing administrative operations which invokesadditional screens that allow for changing passwords and/or user IDs,for defining allowed ranges for stimulation parameters, for registeringa neurostimulator to a particular patient (which can include options forviewing and modifying device information of the neurostimulator 51 a).

An additional selection is a “Login/logout” button control 172 j, andassociated module, for allowing the device 51 b, user/physicianprogrammer 70, or remote user/physician programmer 70′, to establish andterminate communication with each other or with the Management Computer71.

FIG. 10B, shows an embodiment of a menu screen of a computer systemdevice of the system 10, which can be used for setting usage andcompliance parameters. Usage parameter values 176 can be set for maximumand minimum amplitudes used during stimulation as well as the number ofleads through which stimulation is provided (which may be allowed pertreatment credit) and the frequency at which stimulation occurs.Additionally, parameters may include inter-stimulation pauses duringwhich stimulation is not provided, ramping up or ramping down intervalswhich allow for smoother therapy onset and offset in order to deterdisturbing a sleeping subject, maximum duration or # stimulationsallowed for a given interval “dose”, and any of the other stimulationparameter settings or limitations disclosed herein. Settings related tocompliance 178 can be adjusted including, for example, number of daysper week that stimulation should occur during the day (and the minimumand maximum time for each session). In this example, since the maximumamount of time is 2 hours the device may be set to not allow stimulationto occur longer than 2 hours in any particular 24 hour period if a“number of sessions per day” is set to 1. Compliance can also be set forthe number of nights per week that stimulation should occur (and theminimum and maximum time for each session—in this example there is nomaximum time limit). Compliance restrictions may also be related todose-based criteria, for example, a higher amplitude stimulation signalcan be associated with a shorter allowable interval (or total duration“on” over a selected interval) so that the “dose” remains approximatelysimilar. Dose-based compliance relationships can be linear, such asdoubling the stimulation amplitude (or number of pulses provided by aTMS coil) which can result in a halving of the maximum allowableduration or number of stimulation sessions allowed per unit time.Alternatively, strength/duration dose relationships may be non-linearand non-proportional. For example, in the treatment of depression, ifthe neurostimulator includes a TMS coil that delivers “N” pulses of “S”strength, and the user increases the number of pulses to 3N, then S maybe reduced to 90%. The strength/duration, strength/number of treatmentsper unit time, or strength/number of stimulators used to providestimulation, relationships defined by compliance criteria or otherrestrictions related to the provision of stimulation (e.g., defined inthe payments and permissions module) may be defined in various manners.It may be defined by a prescription of a patient that is written by adoctor and realized in electronic form by the system, by findings of asafety study, by the severity of a disorder, by patient response totherapy, according to answers of survey questions, according toimprovement seen during therapy, by drugs taken concurrently as part oftreatment, by the patient's measured tolerance for pain, or otherwiseand may be stored in a look-up table or defined by an equation of theset compliance module 178 which works with the compliance module 200 andother modules of the system.

The treatment session credit field of FIG. 10b shows that there are 60treatment credits remaining prior to the device no longer allowing theuser to provide stimulation sessions. A selection has been made toconfigure the system to cause a decrement of one treatment credit eachday that the user provides at least one stimulation session. If“session” had been selected, then each time the user provided astimulation session lasting longer than a selected amount (e.g. 5-30minutes) then the treatment credit value would be decremented by 1. Ifthe user stops before a minimum time limit (e.g., 5 minutes), then thesession may not count and the treatment credit is not adjusted. Anactivation interval is also shown and the value is 90 days. Thisindicates that the neurostimulator will remain activated for 90 daysfrom the current date. The treatment credit or activation intervalfields may contain values or be left blank. If an interval of activationlimitation is used without a treatment credit limitation, then thedevice will continue to provide stimulation treatment until the end ofthe interval. In an embodiment, in the case where no maximum is definedfor the day/night stimulation fields (e.g. currently set at 3 and 3,where “3+” would signify “at least 3”) then the user would be allowed touse the stimulator as many days as desired before the expiration datedefined by the 90-day interval. There may also be compliance rules setup combination rules that utilize “if”, “and”, and “not” logic, such asa rule which does not allow stimulation to occur during the day ifstimulation was provided the preceding night. In embodiments, the system10 or neurostimulator 51 may be required to check (either periodicallyor before each use) for an active prescription (in a wired or wirelessmanner) to ensure that a doctor intends stimulation to be available.Like the treatment credit information, the prescription data stored in acomputer 71,70′ can also set limits for the maximum number, or length,of stimulation sessions per day. The current settings can be compared tothe prescription if the “check prescription” value is set to “Y”, whichsets an operational flag in the payments and permissions module 202.

An “Alerting” button control 172 k, and associated module, allows forsetting alerting parameter for system components including device 51 b,user/physician programmer 70, remote user/physician programmer 70, canalso be used to alert a patient's smartphone, a customized EXD-pagertype device worn by the patient, or remote Management Computer at aremote site 71 to send an alert (e.g., via e-mail or text message) to apatient to alert to various events including an upcoming therapysession, or to remind a patient if the therapy session was missed.

A “Non-Compliance” button control 172 l, and associated module, allowssetting parameter values and operations that contingently occur due tovarious types and thresholds of non-compliance. For example, alertingmay also be set up to send an alert from the user programmer 70 to aclinic's computer 70′ if the patient is severely non-compliant anddevice usage data meets a non-compliance threshold criterion establishedfor the compliance module 200, for example, the data shows a failure toprovide any therapy over the span of a month.

Another selection that is provided is a “QOL/Diary” button control 172m, and associated module, for allowing setting of operations related toobtaining quality of life (QOL) data and/or bladder diary data. Forexample, survey items for an electronic bladder diary may be presentedto a patient on a defined schedule such as once a week. The data may beprocessed in different manners such as being used to generate summarystatistics and trend graphs related to symptom improvement over time.The QOL/Diary/symptom data may be transmitted with other data to acomputer in a clinic 70′ so that this can be reviewed by a doctor priorto, during, or after a patient's clinic visit. The bladder diary itemsmay be presented to a user visually in textual format with graphicswhere appropriate, or can be presented through a speaker of a deviceusing text-to-voice technology or using pre-recorded messages. Userresponse can be obtained by a user interacting with the neurostimulatoror patient programmer 70 to select a score (e.g. choosing between 1 and7, on a 7 point Likert scale), or by voice, if the device is configuredwith voice-to-text recognition. A user's responses can simply bedigitally recorded and analyzed at a later time by a transcriberservice. The non-compliance criterion can also be defined for theprovision of QOL, bladder diary, or other survey responses data. Userresponse data can occur across 1 or more scheduled sessions. AlthoughQOL and bladder diary information are used in this example, theneurostimulator 51 a can be configured to provide any type of assessmentinstrument or survey items related to a disorder suffered by, orcondition to be modified in, a patient. This may include the assessmentof depression, migraine, memory, pain, sleep apnea, anxiety,hypertension, tremor, concentration/attention/focus, sexual desire orperformance, reaction time, etc.

A “Send to Device” button control 172 n, and associated module, allowsthe user to update the neurostimulator 51 a and/or the programmer 70with the new settings.

A “Send to Memory stick” button control 172 o, and associated module,allows the system to enable the updating of the neurostimulator 51 a byproviding the information on a memory stick that is given to thepatient. When a patient does not want to visit a doctor's clinic anddoes not have access to internet or cellular coverage, or who may not becomfortable operating a computer, a memory stick may be provided whichcan simply be plugged into an I/O port 114 of a device 51 a. This willprovide an update to the device data and allow for continued treatmentof a patient. Routines in the communication module 68 can allow uploadof all device information (including usage and compliance) to the memorystick. This can then be sent back to the doctor's office so device datacan be reviewed.

A “Generate Code/Tones” button control 172 o, and associated module,allow for a code to be generated which can be printed out and sent(mailed/e-mailed) to a patient who can then enter the code into theneurostimulator 51 a or programmer 70 using the user interface module 80in order to allow for continued treatment of the patient. The code mayextend the duration during which the device may be used, or increase thenumber of treatment credits which are present in the device. Inembodiments, instead of a code, a barcode or the like (Data Matrix andQR Codes) can be printed out and the programmer 70 can read the code viaa digital camera in order to re-activate the device. In embodiments, acomputer can use a sonic protocol as is done by facsimile machines cocommunicate with a device 51 a over a phone line, with appropriatemodulation, handshaking, and demodulation implemented within thetransmission protocol.

In an embodiment, operation of the menu screens shown in FIGS. 10A and10B displayed to a user by a computer system, allows patient selectionsthat cause a first processor of the control module 52 of theuser/physician computer 70 to transmit data signals to a secondprocessor of a remote computer 70′ (or 71) which has been configuredwith communication 68 and control 52 modules designed to receive andoperate upon the information data sent from the first processor.Further, the second processor is configured to access information valuesstored in memory 60 such as in at least one table that can be related totreatment of a patient such as: parameter values for a stimulationprogram, treatment credits, activation interval during which the device51 a is permitted to operate, values related to a status or limitationsof a prescription of a patient, compliance data and/or criteria of apatient, payment information of a patient, insurance information of apatient, payment and identification information of a clinic, rights andprivilege information that is related to a user of a neurostimulator,maintenance information related to a neurostimulator, and/or geographiclocation information related to a neurostimulator if the neurostimulator(or other system component) has GPS or uses other geo-locationtechnology.

The information can be operated upon by the processor of the remotecomputer according to algorithms and rules related to compliance,payment, and provision of stimulation therapy by at least oneneurostimulator 51 a. The second computer can then transmit the resultdata of this processing as an information data result to the physiciancomputer 70 in order to select, update, adjust, allow, disallow, orotherwise operate upon the settings that effect operations of aneurostimulator 51 a in a manner that adjusts the provision of therapyfor at least one patient. As is the case for the patient programmer 70and other components of the subject invention, the components shown inFIGS. 10A and 10B can be used for stimulation systems which incorporateTENS and percutaneous stimulators as well as those having fully orpartially implantable stimulators, and systems using implantablestimulators powered by external components. Combination systems can alsobe supported, such as providing TENS from an externally worn controllerwhich also provides power to an implanted neurostimulator.

During a communication session when the neurostimulator 51 acommunicates with the computer 70, a processor can cause information tobe updated and stored in the memory of the neurostimulator 51 a. Thiscan occur contingently based on user input operating the menu screen170. For example, if one or more treatment credits are purchased, or areotherwise renewed (e.g., based upon the user meeting compliancecriteria), then the treatment credits are sent by the computer 70 andreceived by the neurostimulator 51 a processor and the number ofavailable treatment credits is updated in the payment and permissionmodule 202 in order to enable treatment sessions to occur. When theneurostimulator 51 a is in communication with the computer 70 or acomputer system network that communicates, in a wired or wirelessmanner, with the computer 70, then parameter values used by theneurostimulator 51 a during operation (e.g. a permitted range of valuesfor various parameter settings) can be adjusted.

The stimulation treatment regimen may be defined for use with animplanted neurostimulator, and external neurostimulator, or a treatmentregimen that includes the combination. The treatment compliance module200 operations are adjusted accordingly. The determination of whetherthe regimen includes implanted, external, or combinationneurostimulation is adjusted using controls 180.

TENS System and Method Embodiments

Although the SAFN or PTN may be stimulated using genenc TENS stimulatorshaving at least a first and second TENS electrode that can be placed toprovide stimulation of these nerves, recent TENS technology has movedtowards specialized systems which are wireless and which use pads orelectrode arrays and also provide features which promote bettertreatment response and easier patient experience. FIG. 11A shows anembodiment of a system for providing SAFN TENS stimulation of a patient6 which includes at least two adhesive TENS pad electrodes 30 e, 30 fthat are disposed within a leg applicator accessory 220 which may be agarment configured for positioning at least one electrode on the medialupper calf area. The garment maybe a customized sock, wrap, or similartype of shaped garment that can be worn by a user. In this embodiment,the leg applicator accessory 220 serves to position at least two TENSstimulators within the material and along the medial leg surface withthe first positioned approximately several inches below the knee and thesecond located about midway between the first electrode and the medialmalleolus. Although the accessory 220 is shown here forming a sock, theaccessory 220 can be designed extend distally only to a locationcephalad to the medial malleolus and does not need to cover the foot. Alead set 86 c can travel within the garment or be routed along thegarment and communicates the stimulation signals to the electrodes 30 e,30 f from a neurostimulator 50 (not shown), which may be strapped to apatient's leg, worn around the patient's waist, or disposed in a pocketon the top of the accessory 220. The electrodes can operate in a bipolarmanner with electrodes 30 e, 30 f or these can both be referenced to anadditional electrode, which may be on the bottom side of theneurostimulator. Rather than both electrodes being below the knee, onecan be above and the other below as may occur with a knee sleeveelectrotherapy garment with dual electrodes. Typically, when aconductive fabric is used, these should be formed within a garment asspecific, electrically-active areas that are formed to electricallytarget specific anatomical areas so that stimulation can be applied tothe SAFN without stimulating other targets such as calf muscle or thesural nerve on the lateral side of the leg. A shaped area ofelectro-conductive garment 31 is shown around electrode 30 f.

FIG. 11B shows an alternative embodiment of a system for providing SAFNTENS stimulation of a patient 6 which includes at least two adhesiveTENS pad electrodes 30 g,h and 30 i,j (j is not shown) that are disposedwithin each of two upper leg applicator accessories 222 a, 222 b, madeof a formed and/or elastic garment material that can be worn by apatient and which serves to position the stimulators along the medialleg surface approximately at or below the knee to 3 or 4 inches belowthe knee (although in embodiments it may extend to just above the medialmalleolus). The stimulation provided by the embodiment in 11B may besuitable for stimulating the infrapatellar branch of the SAFN, which maybe less comfortable for some users and may also be more difficult toassess with respect to confirming correct placement of the electrodes. Alead set 86 d communicates the stimulation signals from aneurostimulator 51 c which here is shown disposed on the top of theaccessory 222 a (it can be configured to be snapped onto the garment orheld in a pocket disposed in the garment), to the electrodes 30 g, 30 h.An electrode pad 301 is shown on accessory 222 b which communicates toanother neurostimulator (not shown), in order to provide bilateralstimulation. Alternatively, all electrode pads can be connected to asingle neurostimulator using a wire that runs up one leg and down theother. When two neurostimulators are used, they may communicate in awired or wireless manner in order to synchronize the stimulation of bothlegs so that the signals applied to the first and second leg occur at adesired lag, which may be a delay of zero as set by the stimulationprotocol. When a 10 Hz stimulation signal is applied to each leg180-degrees out-of-phase, then the stimulation may be functionallyequivalent to 20 Hz at central nervous locations commonly innervated bythe peripheral signals from each leg.

FIG. 11C shows an alternative embodiment of a system for providing SAFNTENS stimulation of a patient 6 which may be simpler because it does nothave free-standing lead wires. The neurostimulator 51 d can be realizedin a basic embodiment that has only a few controls and no wires. Theneurostimulator 51 d has a first wing 224 a having a top side with afirst control 16 a which is a plus symbol “+” and a second wing 224 bhaving a top surface with a second control 16 b with a negative symbol“−”. The neurostimulator 51 d components are contained within a housinghaving a center region with a battery compartment 228 for accepting atleast one rechargeable or disposable battery 142 which powers theneurostimulator 51 d. The control module 52 of the neurostimulator 51 dis connected to the first and second user interface controls 16 a, 16 b.The user can turn on the device 51 d, under control of the controlmodule 52 by pressing the user interface controls according to definedpatterns. For example, pressing the first and second button 16 a, 16 bfor 3 seconds can turn the unit on and doing this again will turn itoff. The user can increase the stimulation by pressing the first control16 a or decrease the stimulation by pressing the second control 16 b. Inan embodiment, after the device is turned on and connected to a userwith acceptable impedance levels, it will provide a timed stimulationsession which lasts a selected interval such as 30 minutes, after whichthe device may power down. Alternatively, the device may continueperiodically (every 2 hours) provide additional stimulation sessions(e.g., pulse rate 5 to 50 Hz and pulse width 150 μs) as long as itremains connected to a user. The first and second wings are made of aflexible material such as rubber or silicon and have snap connectors 89a, 89 b on their bottom surfaces (that receive stimulation signals by alead set 86 e that resides within each of the first and second wings)which attach to an electrode array comprising two electrodes provided asa reusable adhesive electrode pad that has the same shape as the device51 d and which snaps onto the connectors 89 a, 89 b of the first andsecond wings. Signal transducers for providing alert signaling 156 caninclude a led diode or speaker provided on the top surface of the firstwing in order to notify the user about the start or stop of stimulationtherapy and also can provide a warning alert if either electrode pad isnot attached correctly as can be measured by an impedance module orother electronics that can detect this problem. The unit can use codessuch as “a single long high beep” or “two long high beeps” where high is1000 Hz or a low buzz (500 Hz) if, for example, the power management 74indicates that the battery 142 is low. Voice messages can also be used.A communication module may also be provided to enable the stimulator 51d to wirelessly send and receive data and be controlled by a smartphonewhich can serve as a user/physician programmer 70. Additionally, diodesor an LCD can allow signaling of information such as battery charge.

In order to maintain the neurostimulator 51 d in position at least afirst strap 229 a is provided which is attached to the first wing 224 aand configured to wrap around the calf area to secure the first wing tothe user's leg. Additionally, a second strap 229 b may be provided whichis attached to the second wing 224 b and configured to wrap around thecalf area to secure the second wing to the user's leg. The straps act tosecure the neurostimulator 51 d in position and apply compression tobias each of the wings and the TENS attached to the bottom surface ofeach wing against the user's leg. A strap can also be configured to beattached to the housing of a neurostimulator or an electrode arrayrather than the two wings. The strap is configured with a length andfastening means which allows for the strap to wrap around a legcircumference of between 30 to 48 cm corresponding to that expected inthe calf area of an adult user (McDowell et al Anthropometric ReferenceData for Children and Adults: United States, 2003-2006).

In an embodiment, when the neurostimulator 51 d is configured to workjointly with an implantable neurostimulator which is controlled by anexternal controller, then conduits 86 a conduct energy to power eitherRF or magnetic transmitters to power the implanted device.Alternatively, the RF or magnetic transmitters are located in thehousing of the neurostimulator 51 d and the neurostimulator 51 d isconfigured to also provide TENS either concurrently or at a differenttime that the implantable neurostimulator provides stimulation. Theneurostimulator 51 d can be controlled by a user programmer 70, whichalso controls the implantable neurostimulator either by communicatingdirectly or by working jointly with the neurostimulator 51 d.

FIG. 12 shows an embodiment of a method for performing OAB treatmentsuch as a SAFN stimulation treatment session using a neurostimulator 51a. Various steps may be performed in a different order, omitted, orrepeated. In a general embodiment the steps of FIG. 12 can occur so thatthe device is operated based upon a verification-treatment basis. Thismeans that when one or more defined verification criteria are met,stimulation treatment can be provided to a patient. The verificationstep can simply entail assessing if a per-treatment session paymentcredit is available, and if not then a payment must be made before theneurostimulator 51 a is “verified”. For example, during verification thenumber of stimulation-credits of the system 10 is assessed and must beabove a selected value for verification to be true. Once verified thedevice is granted permission (i.e., set a verification status flag totrue) to provide stimulation. The stimulation treatment credit value isdecremented by a value of 1 either in a device 51 a or in auser/programmer 70 before, during, or after the stimulation is provided.The permission flag may have a time limit such as a subsequent intervalof one hour, 2 hours, one week, or other defined interval. The decrementin treatment credit value may only occur after a stimulator 51 a hasbeen used for a minimum amount of time, such as 7 minutes, to avoidcharging a user for an “incomplete” stimulation session that does notlast a minimum duration. In step 230, a user (patient or physician)obtains a neurostimulator 51 a and performs the additional steps to setup the hardware for providing treatment.

In step 232, a user establishes a user account on the computer system.If the neurostimulator 51 a has not been previously used by the userthen the user can link the neurostimulator 51 a with a user accountand/or user ID. The user ID may be for a clinic when the device is usedin a clinic or may be for a patient who will be treated by the clinic.The User ID can be for a user when the device will be used at apatient's home. Preferably, the payment and permission module 202 of aneurostimulator has, or is assigned, a unique identification number bywhich it is identified during communication/transaction with a computersystem.

In step 234, a user can sign into a user account, navigate to a menu 170and select, for example, a choice of “manage treatment credits” 172 athat enables the purchase of one or more treatment credits. Eachpurchased treatment credit that is uploaded to the physician programmer70, and/or the neurostimulator 51 a preferably includes data and aunique identification number.

In step 236, communication between a neurostimulator 51 a and a computersystem (which may include any of 70, 70′, 71 and communicationtherebetween) is established using wired or wireless communication.Communication can also occur between the computer and a memory stickwhich will then be used to transfer data and credits to theneurostimulator during a separate step. The modules can be stored andoperated on a server computer having a processor and control moduleconfigured to provide user accounts that can also allow management ofuser and device information. The communication can include readingand/or adjustment of initial parameter values that are set for thedevice 51 a at the start of the communication session and finalparameter values that exist at the end of the communication. Step 236can include a step of providing information to a user on a display 174of the physician programmer or on a display 79 of the neurostimulator 51a.

After verification that the neurostimulator 51 a is an authorized device238 that has been associated or “linked” with a particular user accountand/or user ID, in step 240 the computer system transmits one or moretreatment credits that are available or which may be purchased to theneurostimulator 51 a. Alternatively, as has been disclosed, informationcould be transferred between the computer system and the neurostimulator51 a using a digital storage device such as a flash drive as part ofstep 240. In step 240 a code can be generated that is simply manuallyentered or optically scanned into the neurostimulator 51 b by a user andoperation of the payments and permissions module 202 has been previouslyprogrammed to interpret the code to provide appropriate functionality.

Transmission of a purchased treatment credit between an externalcomputing device and the neurostimulator 51 a, can include one-way ortwo-way communication of information related to number of remainingtreatment credits available (if any), the total number of treatmentsessions (and associated times and intervals) which have already beenprovided, or which are scheduled to be provided by the neurostimulator51 a, a count, including details, related to “incomplete” treatmentsessions that did not last longer than a minimum amount (and relateddetails), information related to the use of a particular treatmentcredit based on a unique serial number and any associate informationrelated to a user account, user ID, patient ID, and other operationalinformation. Instead of treatment credits and especially in the casewhere a user of the neurostimulator is used by a patient rather than aphysician, if the device is “verified” due to patient data and/orpayment information meeting all relevant criteria (i.e., a patient hasmet all defined compliance criteria and the patient is paid up throughthe current month, etc) then the device may simply be verified andinformation is sent which allows the neurostimulator 51 a to operate foran upcoming period such as another month, after which the user must“renew” the neurostimulator 51 a.

In step 242, the patient or administrator operates the neurostimulator51 a to provide a treatment session. In step 244, the neurostimulator 51a determines whether the device is “verified” which may simply entaildetermining if a treatment credit is available. However, even if atreatment credit is available, if the patient has not met compliancecriteria or if a prescription for the patient using the device hasexpired then the device 51 a may not provide stimulation. If the deviceis verified then the neurostimulator may provide treatment and performcontingent operations such as managing a parameter value associated withtreatment credits. If it is determined in step 244 that there are nomore available treatment credits or that the device is not “verified”,then the user must return to step 240 to purchase additional treatmentcredits before another treatment session may be performed or the devicemay be otherwise verified.

If a treatment credit is available, and the device is verified then thenerve stimulation 51 a performs a treatment session using one of thetreatment credits purchased and transferred to the neurostimulator 240.In performing the treatment session, the neurostimulator 51 a activatesthe pulse generator so that current pulses of a stimulation signaltraverse the stimulation site during the treatment session by passingbetween stimulators such as from the TENS electrode 88 to thepercutaneous electrode needle 28. If the device is operated on apay-per-session basis then after a treatment session is performed, thenumber of available treatment credits is reduced by one. Step 242 isthen repeated when another treatment session is desired. In embodiments,the system allows for devices to be verified although a treatment creditvalue may be negative reflecting a treatment credit deficit.

Methods for providing therapy are shown in FIG. 13A, where in a firststep 250, a needle electrode is percutaneously inserted in the leg at orbelow the knee at a position known, or determined to be, appropriate forstimulation of the SAFN.

In a second step 252, an assessment procedure is performed wherein thesignal provided by a neurostimulator 51 b is increased in steps (e.g.,0.5 uA, 50 uA, or 0.5 mA) from a starting value to a value at which thepatient experiences tingling, warmth, pressure, vibration or othersimilar sensory event which has been determined to indicate that theSAFN is stimulated. It is expected that this typically should include asensation that radiates away from the site of the electrodes and oftenwill spread down the leg and even towards the hallux medial malleolus,ankle, or into the foot, or toes (or up the leg if a stimulator islocated near the foot). The stimulation level is then increased fromabove nerve recruitment threshold to a level that is greater but notpainful to the subject and is provided during treatment. If the patientis not able to feel “tingling”, or if it occurs at an amplitude that ishigher than what is expected for that patient (compared to previoussessions of that patient) then the needle electrode may be re-orientedor inserted in a new location, and the assessment is repeated. Thestimulation is then typically halted while the assessment is done forthe PTN stimulation site. An assessment mode of the device may providean assessment signal which increases its amplitude or pulse width toallow the patient to better sense the electrical recruitment of a targetnerve.

In some embodiments for combined SAFN and PTN stimulation, a step 254may be done in which a needle electrode is percutaneously inserted inthe foot or leg at a position known, or determined to be, appropriatefor stimulation of the PTN.

In step 256, the signal provided by the second neurostimulator 51 a (ora second stimulus generator of neurostimulator 51 b) is increased insteps from a starting value to a value at which the patient experiencesa foot motor response which indicates that the PTN is stimulated. Thatlevel is the used to adjust the stimulation amplitude that is providedduring treatment. If no foot twitch is seen or measured from a sensor,or if the subjective sensation of a muscle response occurs at anamplitude that is higher than what is expected for that patient then theneedle electrode is removed, inserted in a new location, and theassessment is done again. After a successful location is found thestimulation can then be halted for the PTN stimulator until combinationtreatment is initiated.

In the fifth step 258, combination stimulation is provided to both theSAFN and the PTN according to a selected therapy protocol whereby thesignals for the first and second stimulators are provided and therapycontinues for the selected therapy interval. For example, thestimulation may alternate between the SAFN and the PTN, may occursimultaneously, or may occur as otherwise designed. A variant of thismethod can include using two stimulation sites which are both SAFN.Sites can be selected on the same or different leg. Although this methodis oriented for percutaneous stimulation, a similar method can be usedfor combination TENS therapy (or other type of stimulation) where thestimulation of the SAFN and PTN are assessed separately beforestimulation therapy is provided.

As shown in FIG. 13B, in a first step 260, at least a first TENSelectrode is attached to a subject's leg at a position known, ordetermined to be, appropriate for stimulation of the SAFN, while atleast a second TENS electrode is placed nearby, preferably lower on themedial surface of the leg or at a location such as the inner sole of thefoot.

The TENS approach to electrically stimulating the SAFN for the treatmentof OAB will typically involve placing at least one pair of surfaceelectrodes placed on the medial aspect of the lower leg (e.g. step 260of FIG. 13B), with one electrode slightly below the knee. Placement ofthe electrodes may target the SAFN branches that travel subcutaneouslyfrom the level of the knee down to the ankle but electrodes on themedial aspect of the sole of the foot may also be found to provideeffective bladder modulation. Anatomical studies in human cadaversreport a high degree of variability in the anatomical location of theSAFN branches (Wilmot, V. V. and Evans, D. J. R. (2013), Categorizingthe distribution of the saphenous nerve in relation to the greatsaphenous vein. Clin. Anat., 26: 531-536). As such, the optimalelectrode configuration may vary from one patient to another. Ingeneral, the SAFN emerges as either single or multiple fascicles at thelevel of the knee, immediately posterior to the medial condyle of thetibia. These travel along the medial aspect of the leg and can belocated either anterior or posterior to the saphenous vein.Anatomically, the saphenous vein is located along the posterior marginof the tibial bone. Therefore, the main SAFN may be located moreanterior or posterior to the posterior margin of the tibia. Placing theelectrode too posterior to the tibia may result in the electrode beingdirectly over the medical gastrocnemius muscle, which may beelectrically activated during stimulation. This unintended muscleactivation may cause discomfort to the patient. If this occurs, theelectrode should likely be repositioned and stimulation tried again toavoid this.

In a second step 262, an assessment procedure is performed wherein thesignal provided by a neurostimulator 51 b is increased in steps from astarting value to a value at which the patient experiences a tinglingsensation radiating along the leg which indicates that the SAFN is beingmodulated. That level can then be used to adjust the stimulationamplitude that is provided during treatment 266. If the patient is notable to feel the expected sensation, or if it occurs at an amplitudethat is higher than what is expected for that patient (compared toprevious sessions of that patient) then at least the first TENSelectrode is removed, applied to a new location on the medial aspect ofthe leg, and the assessment is repeated. Rather than moving a singleelectrode, an electrode array or neurostimulator having pairs ofelectrodes can be moved or stimulation elements of the array may beselected to change the spatial stimulation area.

During assessment of the SAFN 262, a doctor or patient may be instructedthat correct electrode placement and electrical stimulation of the SAFNmay be determined if a patient can confirm a “tingling” sensation thatradiates below the site of stimulation. If stimulation evokes a footmotor response, then the selected electrode placement and/or selectedstimulation signal may be (co-)activating the tibial nerve. In thiscase, it may be beneficial to change the location of one or moreelectrodes and re-assess.

With respect to adjusting stimulation characteristics 266, amplitude istypically set at the maximum value that is tolerated by the patient inthe case of PTNS treatment. This may also occur in SAFN therapy, or theSAFN stimulation protocol may be distinct. For example, the protocol mayinstruct a user to determine the maximum stimulation and then reduce theamplitude by 10%, 20% or 50%, as long as nerve activation still occurs.In order to ensure that TENS is effective, it is likely that the minimumamplitude used for treatment will be defined by the amplitude at whichthe electrodes (e.g., location 29 b) evoke a sensory percept thatspreads away from the distal electrode down the leg. This indicates thatthe subcutaneously located SAFN fascicle(s) are activated by the TENSelectrodes.

In an embodiment, at least one surface electrode will be placed withinthe upper one-third of the lower leg to target the main fascicle(s) ofthe SAFN. The return electrode may be placed at more distal locations,such as the mid-point between the knee and the foot (29 d or anterior tothis location), 5 cm cephalad to the medial malleolus (29 c), or themedial aspect of the sole of the foot (location 88). When stimulationcharacteristics of the signal are adjusted 266, polarity can be assignedas part of the stimulation protocol. The polarity of each electrode maybe set to positive (anode) or negative (cathode), or this may beadjusted depending on the preference indicated by the patient based uponsubjective comfort, or this may change during the stimulation.

In the fifth step 268, stimulation is provided to at least the SAFN ofone leg according to a selected stimulation protocol for the selectedtherapy interval such as 30 minutes. The method can also perform theassessment or treatment bilaterally or choose the leg that showsstronger recruitment of the SAFN or its branches.

FIG. 14 shows a system 8 a for providing TENS stimulation including anelectrode array 270 having three TENS electrodes 30 j,k,l which areconnected by conduits 85 a,b,c to three connector sockets 272 a whichreside within a receptor base 274. Rather than connector sockets aconnector can contain routing circuitry and other electronics which canbe under control of the neurostimulator 50 a or the programmer 70. Afirst strap 276 can be configured as first 276 a strap portion andsecond 276 b strap portion which are connected to the array 270 on theirproximal ends and which have fastening portions on their distal ends(e.g. Velcro) or which may be made of a sports wrap type material thatallows the strap portions to grip each other without sticking to the legof the user 6. A second strap 278 may also be provided on the bottom endof the array 270. Rather than being connected permanently to the array270 the straps can be configured to snap onto the array. The receptorbase can be formed of plastic or rubber and is shaped to receive aneurostimulator 50 a which snaps into the connector sockets 272 a so asto reversibly attach the neurostimulator 50 a to the electrode array270. In an embodiment, the array is fabricated using foam, silicone, orrubber material which is flexible and which provides for routing of theconduits 85 to the TENS electrode pads 30. The view shown is the topside of the array 270 and the bottom side is disposed with 3 areas ofelectrode hydrogel or conductive material provided on the TENSelectrodes for connecting to the user's skin. There is also provided auser/physician programmer which may be realized as a smartphone on whicha software application has been downloaded or by a customized userinterface device (a battery powered remote control) which communicateswith the neurostimulator 50 a or electronics provided on the array 270in a wired or wireless manner. When provided as a kit, the array 270,neurostimulator 50 a, programmer 70, and instructions for use 276 may beincluded. In an embodiment, the array 270 is designed to be disposableand provide for approximately 1 month of use.

In an embodiment, the stimulation protocol can stimulate by referencingthe first TENS electrode 30J to the second and third electrodes 30 k,lif the patient can tolerate this. Alternatively, combinations ofstimulation circuits which include electrodes 1 and 2, 2 and 3, 1 and 3,or 1 referenced to 2 and 3 (or 2 referenced to 1 and 3) can be selectedbased upon patient comfort or the success of different electrodecombinations to recruit the SAFN and produce a tingling sensation thatradiates down a subjects leg from the upper-calf where the array ispositioned during use. Allowing a user to selectively and programmablyactivate unique pairs from the 3 electrodes based upon user input canallow a patient to select a stimulation montage that stimulates the SAFNwithout having to physically remove and replace the array to obtainsuccessful positioning of electrodes. It also may be that in somesubjects increasing the size of the electrode field serves to recruitmore nerve branches/fibers, while for others only 2 electrodes workbetter. In an embodiment, only two TENS electrodes (or more than 3) areprovided on the array. Electrode combinations can be determined duringassessment 262.

FIG. 15 shows front and back views of a neurostimulator 50 a on the topand bottom of the figure, respectively. The front side of theneurostimulator shows a display 79, a power button 14, a menu control18, and dedicated buttons 16 which may be used for example, to increaseor decrease stimulation amplitude. Interface port 114 allows forpowering the device or for wired communication with other systemcomponents. The back view shows three connector sockets 272 b whichconnect to the corresponding sockets 272 a on the neurostimulator.Although the neurostimulator 51 b shown in FIG. 2 only has one connectoron its bottom surface for connecting to a TENS electrode, the other 2connectors can simply be inactive during percutaneous stimulation whenthat stimulator is designed to be used for providing therapy bothpercutaneously and transcutaneously.

In this system patients can begin OAB treatment by receivingpercutaneous stimulation in a clinic for a number of sessions and thenthe neurostimulator can be used by the patient to provide TENS byinterfacing with an electrode array. While the treatment credits can beused to manage in-clinic percutaneous stimulation, these can also allowfor a month of TENS treatment per credit, when the neurostimulator isused at home by a single patient rather than in the clinic by multiplepatients.

Kits and Methods for Providing TENS of the SAFN for OAB Treatment.

In an embodiment, the invention is realized as a kit having at least twoTENS electrodes 88 configured to receive a stimulation signal from aTENS neurostimulator 50 a. The stimulation signal can be providedaccording to a stimulation protocol that is defined for stimulation ofthe SAFN for the treatment of overactive bladder. The kit also includesinstructions 276 for using the neurostimulator for the treatment ofoveractive bladder disorder which includes instructing a user to applyat least one of the 2 stimulators on the medial aspect of the leg belowthe knee such as for the treatment of OAB by electrical stimulation ofthe SAFN. In instructions 276, it may alternatively include instructionsto place at least one of the two TENS electrodes on the inner side ofthe leg in the area near the upper calf and then provide a stimulationsignal to determine if at least one of a tingling, vibrating, buzzing,pressure, electrotactile tactile sensation, warmth, or ticklingsensation (or other paresthesia) is experienced as radiating away fromthe location of at least one of the two electrodes. Further, theinstructions direct a user in the case where the sensation is notexperienced, and the application of the stimulation signal fails toproduce a radiating sensation indicating that the SAFN has beenstimulated, then performing the step of either increasing thestimulation signal or adjust the position of at least one of the twoTENS electrodes. In the case where the sensation is experienced thenprovide a stimulation session using a stimulation strength that does notcause pain.

In one embodiment, determining if a sensation occurs includesdetermining if the sensation is radiating away from an electrode anddown the leg towards or into the foot. Alternatively, instructions mayalso include directions to place a second lower electrode near themedial malleolus or the sole of the foot and determining if a sensationoccurs includes determining if the sensation is either radiating awayfrom the first electrode and down the leg, or away from the second lowerelectrode an up the leg.

The instruction 276 can include or be provided on paper or as part ofthe user interface module which has multimedia ability for providinginstructions via the neurostimulator 10 a or the programmer 70.

In an embodiment, the at least two TENS electrodes can be realized aspart of an accessory such as a garment or an electrode array thatpositions the electrodes on the medial aspect of a patient's leg with atleast one electrode positioned approximately 1-4 inches below thepatella or within approximately 1-4 inches of the medial condyle of thetibia.

An external patient programmer can be configured to communicate with andprovide user control of the neurostimulator and at least one of theneurostimulator and external patient programmer are configured tomonitor usage and assess compliance with respect to a treatment programthat is related to treatment of overactive bladder and to providepatient alert reminders related to a stimulation program that is definedfor the treatment of overactive bladder.

In an embodiment, the stimulation signal is defined to be a pulse trainmodulated at 10 Hz, 20 Hz, or can be a signal that roves between 10 and20 Hz. The stimulation signal may be defined to be at least one of:slightly above (e.g. 0.5 or 1 mA) skin threshold (Tskin) which is thelevel at which the stimulation is first felt and slightly below maximumtolerance (Tmax) which corresponds to the level at which a userexperiences discomfort or pain. A signal may also be defined to rovebetween Tskin and Tmax, by continuously or periodically adjustingamplitude, stimulus pulse width, and/or period as may be defined for asinusoidal waveform.

In an embodiment, a system component such as the neurostimulator orprogrammer determines the therapeutic protocol for a given week orlonger periods using a pre-defined schedule stored in its memory. Theschedule may be modified according to various factors such as time sincethe first therapy session, number of stimulation sessions provided sincethe start of therapy, rate of stimulation sessions provided since thestart of therapy. Additional adjustment may be made based uponassessment of patient input data which indicates improvements,worsening, or no change in symptoms as calculated upon patient inputdata.

In embodiments, at least one system component operates at least oneaccelerometer and is configured to analyze the accelerometer data todetermine if a user is active or ambulatory using at least one ofactivity data and orientation data. The accelerometer data maybeanalyzed to determine if the patient is, for example, walking, gettingout of bed, moving with a gait that is over a selected rate. In thiscase, a modification to the system may adjust operation such as pausingor decreasing the provision of stimulation until the accelerometer dataindicates that the user has stopped being active (e.g. the data remainsbelow a selected movement threshold for a selected interval).

In embodiments, the instructions may also incorporate methods andguidelines reviewed in other parts of this specification. Additionally,because SAFN stimulation at the level of the knee can be used to treatindividuals with pain, the kit may be indicated for providing relieffrom both pain and OAB symptoms. In this instance the instructions thatare provided within the kit may instruct a user select the treatmentmode related to the desired therapy and may also instruct to positionelectrodes or an electrode array differentially.

In an embodiment, a method of treating an overactive bladder of a personsuffering symptoms of the disorder includes the steps of applying TENSelectrodes for stimulation 260 which can include establishing at leasttwo transcutaneous electrical neural stimulation (TENS) electrodes 30and establishing a neurostimulator 10 a configurable to provide atreatment stimulation signal to the TENS electrodes according to astimulation protocol that is defined in, or selectable using, astimulation module 54 for stimulation of the SAFN for the treatment ofthe patient's OAB symptoms. This also includes positioning at least oneof the two TENS electrodes on the inner side of the patient's leg 6 inthe area near the upper calf. An assessment procedure 262 can includethe steps of actuating said neurostimulator 10 a to provide a teststimulation signal and assessment to determine if at least one of atingling, vibrating, buzzing, pressure, electrotactile tactilesensation, warmth, or tickling sensation is experienced which radiatesaway from the location of at least one of the two electrodes. In theassessment 262 two steps may occur which include (1) when application ofthe test stimulation signal fails to produce a radiating sensationindicating that the saphenous nerve has been stimulated, then performingthe step of either increasing the test stimulation signal or adjustingthe position of at least one of the two TENS electrodes and (2) when thetest stimulation signal produces the radiating sensation, then providingstimulation treatment 268 using a stimulation signal strength which isnot painful to the patient. The strength can be iteratively assessed oradjusted during therapy in the case that the patient's threshold forpain changes.

In the method, the step of determining whether a sensation occurs mayinclude the step of determining if the sensation is radiating away froman electrode and down the leg towards or into the foot. Alternatively,the application step may include the steps of providing instructions toplace, or placing, a second lower electrode so that it is verticallydisplaced from the first electrode and near the medial malleolus or thesole of the foot and determining if a sensation occurs which can beeither radiating away from the first electrode and down the leg, or awayfrom the second lower electrode and up the leg. The term “verticallydisplaced” signifies that one electrode is offset longitudinally along alimb relative to another i.e., it is more caudal or distal.

The method may also include the step of providing user instructions, orinstructing a user directly, and these can be related to actuating saidneurostimulator to provide a test stimulation signal and performassessment 262 and providing stimulation with various protocols 268. Theuser instructions can include at least one of: written instructions;illustrations of the leg with graphical depictions of the location onthe medial surface of the leg where the TENS electrodes should beplaced; illustrations of the leg with graphical depictions of thelocation on the medial surface of the leg where a TENS array should beplaced; instructions provided by a mobile device app or a mobile device;an audio-message of instructions; verbal instructions; instructions touse a device such as an ultrasound, infrared, or electrical impedancedevice in order to locate the saphenous nerve or saphenous vein;instructions provided in combination with either a virtual reality orholographic display; instructions provided by a mixed media technologysuch as a DVD, and, a website address where user instructions areprovided. User instructions include directions to use landmarks such asanatomical landmarks or markings made on the skin (e.g. tattoo) thatindicate the positioning for at least one TENS electrode.

In the method, at least two TENS electrodes can be realized as part ofan accessory such as an electrode array 270 that positions theelectrodes on the medial aspect of a patient's leg, or a garment 220.Additionally, when the at least two TENS electrodes are realized withinan electrode array 270 that is designed to be connected to at least oneband 276 that is configured to be wrapped around the calf of a patientand to position the array vertically along the inner side of the leg andthe first electrode is above the second electrode. The band may beconfigured to wrap around the area of a patient's upper calf to secureand bias the electrode to the calf. The band or garment 220 can beconfigured to be attached to at least one electrode and to wrap aroundthe area of a patient's upper calf, mid-calf, or entire leg to secureand bias the one electrode to the area between the upper calf muscle andthe tibia.

The method may further include providing or operating an externalpatient programmer 70 which is configured to communicate with andprovide user control of the neurostimulator and at least one of theneurostimulator and external patient programmer are configured tomonitor usage and assess compliance with respect to a treatment programthat is related to treatment of overactive bladder and to providepatient alert reminders related to a stimulation program that is definedfor the treatment of overactive bladder. Additionally, at least one ofthe neurostimulator and external patient programmer are configured witha user interface module 80 configured to query about bladder activity,bladder pressure, urinary leakage and/or urgency episodes measured bywearable or implantable sensors. In an embodiment, at least one of theneurostimulator and external patient programmer are configured to querythe patient about a symptom characteristic such as urgency, urgeincontinence or frequency related to overactive bladder symptoms and tostore the responses. Further, at least one of the neurostimulator andexternal patient programmer are configured to allow the patient to inputinformation related to a bladder diary, including if a void event wasassociated with urgency or leakage. These may also be configured toquery the patient to input information about whether any voiding eventsoccurred during sleep, whether voiding events awoke the patient, orwhether voiding events were accompanied by urgency and/or leakage.

The method can further include setting, instructing, or providinginstructions related to setting a stimulation protocol that is definedfor stimulation of the SAFN for the treatment of OAB which includessetting the stimulation signal to be at least one of: a signal between 5and 20 Hz, a 10 Hz signal, a 20 Hz signal, and a signal that rovesbetween 10 and 20 Hz. The stimulation signal can be defined in thestimulation module 54 to be at least one of: skin threshold (Tskin),maximum tolerance (Tmax), and a signal that roves between Tskin andTmax, by continuously or periodically adjusting amplitude, stimuluspulse width, and/or period in the case of a sinusoidal waveform.

The method can also include an external patient programmer 70 that isfurther configured to graphically display data related tooveractive-bladder-related symptoms as summary statistics or trendcharts. The external device or programmer 70 can also determine thetherapeutic protocol for a given week or longer periods using rules orlookup tables of the compliance module 200 based upon factors such astime since the start of therapy, number of stimulation sessions providedsince the start of therapy, rate of stimulation sessions provided sincethe start of therapy, and improvements, worsening, or no change insymptoms as calculated upon patient input data.

The method can also include providing and operating an accelerometer forat least one system component and the system 10 a is configured toanalyze the accelerometer data to determine if a user is active orambulatory by using at least one of activity data and orientation data.The accelerometer data may be analyzed to determine whether the patientis, for example, walking, getting out of bed, moving with a gait that isover a selected rate. In this case, the system may modify operation suchas pausing or decreasing stimulation until the accelerometer determinesthat the user has stopped being active.

In an embodiment a system for transcutaneous electrical nervestimulation in humans includes a housing 12 a stimulation module 54having stimulation generator mounted within the housing for electricallystimulating nerves and an electrode array 270 releasably mounted to thehousing and connectable to the stimulation generator, the electrodearray comprising a plurality of at least two electrodes 30 forelectrical stimulation of nerves. The user interface module 80 canprovide at least one user control 16 mounted to the housing andelectrically connected to a user interface module 80 working with thecontrol module 52 to control the stimulation generator for controllingat least one characteristic of a stimulation signal generated by thestimulus generator. The sensing module 55 can provide monitoringcircuitry mounted to the housing 12 and electrically connected to thestimulation means for monitoring impedance in order to assess electrodecontact with patient skin 6. A user interface module 80 mounted withinthe housing 12 and electrically connected to the control module 52 forcontrolling the stimulus generator. A user display can be part of theinterface module 80 and mounted to the housing and electricallyconnected to the control user interface module 80 and the monitoringcircuitry of the sensing module 55 for displaying the status informationrelated to the device 50 a. At least one strap 276 can be attached to atleast one of the housing and the electrode array 270 and the strap isconfigured to hold at least one of the housing 12 and the electrodearray 270 so that the array stimulates a specific anatomical location totreat OAB by stimulation of the SAFN using at least two longitudinallydisplaced electrodes 30. Preferably, the location is the medial surfaceof the upper calf area between the calf muscle and the tibia.

In an embodiment, a treatment regimen compliance system has a controlmodule 52 with a processor configured for providing the controloperations to occur according to a treatment regimen. The treatmentregimen includes a treatment schedule with days and times related towhen therapy events are scheduled to occur such as the provision ofstimulation, taking of medication, surveying of the user with selectedsurvey materials, presentation of videos that may reinforce healthyhabits, behaviors, or cognition, use of digital health tools such assoftware programs that engage the user and which relate to therapy forvarious disorders, and even the presentation of digital games thatreinforce concepts related to therapy. At least one neurostimulator 50a,300 is functionally coupled to the processor and configured tocommunicate data or control signals to and from the processor. Forexample, the neurostimulator may keep a log of use and can communicatethis log to the control module so that the compliance module can updatethe history of therapy and evaluate the history to determine if one ormore compliance criteria are being met. The processor can be part of theneurostimulator 50 a or exist in other system component such as theuser/physician programmer 70. The control module 52 is configured toaccess an established treatment regimen for a patient, or allow theestablishment of a programmable treatment regimen and to control acompliance module that is configured for calculating a measurement ofcompliance for at least one characteristic of the programmable treatmentregimen. The programmable treatment regimen is defined for at leastneurostimulation provided by at least one neurostimulator 50 a. Further,at least one user notification module 360 which operates as part of theuser interface module 80 is functionally coupled to the control module52 and configured to provide a notification signal to a user related tocompliance of the programmable treatment regimen. The notificationsignal is sent responsive to at least one notification rule. The systemalso includes at least one external patient/physician device 70configured to present notification signals, accept user input data, andcommunicate data or control signals with the processor. The compliancemodule 200 is realized as a module of a neurostimulator 52 a,patient/physician device 70, or other system component 70′ and can berealized as distributed across both the neurostimulator andpatient/physician device.

In an embodiment, as shown in FIG. 16, in step 302 a treatment regimenis established or updated which includes regimen parameter valuesrelated to, for example, when treatment events occur or how many of aparticular treatment event should occur. The treatment regimen defines aminimum required or maximum suggested dose of stimulation to occur overan interval, such as 30 minutes at least twice a week. Alternatively,the regimen is defined more specifically such as including a treatmentschedule associating particular days and times with treatment events.The compliance module 200 analyzes data in the programmer 70 orneurostimulator to assess compliance for a given compliance measurement.For example, a neurostimulator 50 a is functionally coupled to theprocessor and configured to communicate data which is analyzed by thecompliance module 200. The neurostimulator 50 a keeps a log abouttreatments it has provided which is communicated to the control module52 so that the compliance module can update and assess the history oftherapy for a user. The control module 52 operates the compliance module200 according to triggers 303. For example, the triggers can occurperiodically, when a therapy event occurs, or is scheduled to occur inthe near future (e.g. 1 hour in the future), or in a time/scheduledmanner so that it evaluates the history of treatment events to determineif one or more compliance criteria are being met 304. When thecompliance module calculates a measurement of compliance for at leastone characteristic of the programmable treatment regimen, thencontingent operations occur 306.

The compliance module 200 is configured to operate according tocompliance rules defined for contingently modifying system operations306, such as the operation of a neurostimalutor, user/physicianprogrammer, or other system component based upon assessment ofcompliance 304. For example, various operations are defined contingentlysuch as compliance operations 307 a that occur when one or morecompliance criteria are met and non-compliance operations 307 b whichoccur when one or more non-compliance criteria are met. A contingentstep may be defined to occur both in the case where a compliancecriterion is met or where a non-compliance criterion is met. Forexample, in step 308, a next scheduled treatment event may berescheduled in the case where a stimulation treatment session was notprovided by a user within 2 hours of the scheduled time. Alternatively,step 308 can cause a scheduled stimulation session scheduled for thelate afternoon to be cancelled if a user provided a stimulation sessionearlier on that same day. In step 308 the earlier stimulation sessionwould permit the compliance criterion to be met and also prevent areminder alarm from being triggered later in the day at the time of theoriginally scheduled treatment session. In step 309, counters and flagsare set, reset (i.e., cleared), or updated in the user log of memorymodule 60 so that the compliance criterion are evaluated as true orfalse according to the current status. A historical record of flagparameter settings is also be updated in the user log in this step. Instep 310 compliance status for at least 1 characteristic of thetreatment regimen is calculated and displayed. For instance a scheduledtreatment for a particular day may be given a status of compliant if thepatient has provided stimulation above a minimum threshold value.Additionally, in step 312 summary statistics for compliance ascalculated across multiple treatment events are derived and displayed.

The evaluation of compliance and non-compliance criteria may occur usingrules defined in look-up tables, algorithms, equations, and can combineacross multiple criteria using Boolean logic. For example, anon-compliant contingent operation may be defined as part of a rule ofstep 307 b which triggers a subroutine of step 311, which includesecosystem support operations such as presenting a short video to thepatient on the importance of compliance. This may be triggered only if atreatment criterion requiring a minimum of three stimulation treatmentsa week is not met AND also this criterion was not met for the priorweek.

The control module the implements step 314 where a notification rule isassessed by a notification module 360. If the rule determines thatnotification should be sent according to a notification rule, then anotification signal is provided to a user 318 that is related tocompliance status. The notification signal is sent responsive to atleast one notification rule, for example, the rule may specify that ifnon-compliance exceeds a selected threshold then a notification is alsotransmitted to a doctor, insurance company, or medical service, ratherthan only to the patient. The notification can occur using the externalpatient/physician device 70 that is configured to present notificationsignals, accept user input data, and communicate data or control signalswith the processor, can be provided on the neurostimulator 50 a, and/orother system components. The notification module 360 operates at leastpartially under control of the compliance module based upon assessmentof at least one parameter defined for treatment regimen operations orevents according to the notification rules. Alternatively, if the ruledoes not dictate that notification should be sent step 322 occurs wherethe history treatment events (e.g. stimulations, notifications, surveys)and compliance flag status's are updated and housekeeping of parametersvalues occurs.

In an embodiment, a parameter defined for treatment regimen that isassessed in step 304 is a compliance measurement that assesses whether adefined stimulation dose (e.g. a duration of stimulation using at leasta minimum stimulation amplitude) has been provided within a selectedtime interval. For example, two stimulation sessions each lasting atleast 30 minutes have occurred over a prior interval such as the pastweek. Alternatively, the compliance measurement 304 assesses complianceabout whether a defined set of questions has been provided and thenanswered sufficiently to meet a criterion (e.g. questions about bladdersymptoms such as bladder urgency were answered within a selected timeinterval such as 10 minutes from when the user was prompted and/or atleast a percentages such as 75% of the questions were answered).Alternatively, the compliance measurement 304 evaluates compliance forplaying/viewing a defined set of training videos, multi-media clips, orverbal or textual instructions and reminders. If a criterion such asthat one or more of these should be provided to the user at least 3times within a selected time interval such as the first 2 weeks oftreatment then in step 311 a video may suggested to the user. Trainingvideos include use of a neurostimulator during treatment (e.g.,application of electrodes, setting stimulation signal parameters, how touse features of the software, such as video-conference with medicalservice support (and what to expect), replacing disposable components,etc) or management of a disorder. In the case of overactive bladder, thevideos may promote lifestyle changes such as drinking less beforebedtime, anxiety, the videos may be designed to promote relaxation. Inthe case of depression, the videos can provide cognitive behavioraltherapy. In the case of non-compliance, after a user is provided with anotification 318, the user can then be prompted to correct thenon-compliance such as by allowing a non-compliance operation to occur324, such as viewing a video, providing treatment, etc. as provided bythe multi-media module 366. Training videos may also be supplied by theecosystem module 368 which provides ecosystem features such as videoinstruction, virtual meetings, lifestyle reminders and other features incollaboration with other modules of the system. In the case where a userprovides an amount of stimulation that exceeds maximum suggested dose,the non-compliance operation that is contingently invoked is that avideo may be presented to the user that explains harm that may occur dueto exceeding the recommended stimulation dose such as skin irritation orbladder retention in the case of treatment of OAB. The video may bepresented on the programmer 70, or may be viewed on a smart-TV whichsends a signal to the communication module 68 of the system so that thistherapy event is registered. Similarly, if the video is requestedthrough a voice service (e.g. Alexa) to be viewed by a user, then thesystem may communicate with the accessory providing the voice service inorder register the occurrence of the therapy event.

In an embodiment, another parameter defined for treatment regimenoperations for which a compliance measurement is assessed 304 is for adefined set of messages about lifestyle changes that is scheduled to beviewed a selected number of times within a selected time interval. Forexample, during the first month of therapy which serves as an inductionperiod, the regimen has a parameter value that is set which dictatesthat treatment includes viewing messages concerning lifestyleadjustments conducive to treatment benefit (e.g. avoiding coffee) atleast twice a day. This parameter value can be can increased ordecreased depending upon changes in symptoms that are input to thesystem as user input data over time.

In an embodiment, another measurement of compliance that occurs in step304 relates to at least one characteristic (e.g., duration ofuninterrupted stimulation, stimulation signal amplitude, stimulationprovided during sleep) of a programmable treatment regimen for at leastone neurostimulation treatment defined in the regimen for at least oneneurostimulator, and includes determining if a compliance criterion hasbeen met which includes a minimum stimulation dose delivered across aselected time interval or a minimum number of treatment sessions (e.g.,3) lasting minimum defined period (e.g., 30-180 minutes) have beendelivered within a selected interval (e.g., one week).

In an embodiment, the notification rules, definitions of compliance andnon-compliance criteria, contingent operations, and rules to assessmeasurements of compliance and non-compliance of at least onecharacteristic of a programmable treatment regimen occur usingoperations and parameter values defined in one or more lookup tables.The compliance measurement definitions allow for determining, forexample: compliance in not exceeding maximum number of treatmentsessions lasting a minimum defined period within a selected interval;compliance in not exceeding a maximum defined dosage within a selectedinterval; compliance in alternating stimulation sites between the twosides of the body or two sites after a selected interval of stimulation,as defined by a stimulation location criterion; compliance in replacingdisposable stimulation pads within a selected interval, as defined by areplacement of disposables criterion; compliance in executing ascheduled a doctor visit at a clinic or a virtual visit using aweb-meeting medical assistance module 362 within a selected interval, asdefined by a check-up criterion; compliance in performing a minimumnumber of defined behaviors such as such as performing kegal exercises,electrically assisted intravaginal stimulation, within a selectedinterval, as defined by a user behavior criterion; compliance withrespect to a medication regimen that is intended to occur over the sametime period as the neurostimulation, as defined by a medicationcriterion; compliance with respect to a digital health regimen thatincludes being engaged daily or weekly using digital health softwareprograms, as defined by a digital health tools criterion; compliancewith respect providing stimulation within selected intervals ofscheduled treatment times, as defined by a latency criterion; and,compliance with respect providing stimulation according to a minimumnumber of scheduled treatment times that are scheduled to occur atnight, as defined by a therapy criterion.

In an embodiment, the measurement of compliance 304 is forneurostimulation defined for at least one neurostimulator, and includesdetermining if a compliance criterion has been met for at least onestimulation session and graphically displaying a status result thatindicates whether the criterion was met or not as defined in thecompliance operations 306.

In an embodiment, the measurement of compliance 304 includes determiningif a compliance criterion has been met relating to a treatment regimenoperation that occurs contingently based upon at least one of thefollowing: according to a calendar schedule, or according to thepresence, absence, severity, change, or trend of patient symptoms. Achange or trend in patient symptoms is evaluated for a history of atleast one reference data value such as provided by user input or senseddata. The compliance criterion can also be assessed according to both acalendar schedule and symptom changes from a previous period. Forexample, compliance to the calendar schedule is assessed with more“relaxed” criteria (e.g. allowing for a greater number of scheduledstimulation treatments to be missed before non-compliance flagged by thesystem) if a patient has experienced a larger improvement from baselineand will still experience symptom improvement even if not fullycompliant with treatment.

In an embodiment, the measurement of compliance 304 is evaluated forreceiving user input data to or more questions contingently presented toa user for example, based upon history of symptom improvement, timesince beginning the course of treatment, or the combination.

In an embodiment, parameters that are defined in the compliance moduleare adjusted contingently upon whether the user provides or fails toprovide a treatment event (e.g. a stimulation treatment) that meets aschedule or in response to a notification signal. For example, theschedule of the treatment regimen that defines scheduled doses ofneurostimulation can be adjusted in step 308 according to whethertreatment was provided by the user. For example, a missed scheduledtreatment session can be rescheduled so that a dose is still realized,or if a session is provided by the patient earlier than that scheduled,the scheduled session can be cancelled. Accordingly, the provision ofuser notification to prompt stimulation under control of the compliancemodule for the later session is cancelled so that this does not annoy auser unnecessarily. In the event of a missed or incomplete treatmentsession, the compliance module may provide reminder alarms, reschedulefor next day, notify the user that they provided stimulation that wasinsufficient to meet a dosage or session criterion and it will berescheduled. Further, a compliance criterion relate to dosage mayimplement a substitution rule that relies upon total dosage over time.For example, if a user provides 60 minutes of stimulation instead of 30,and the stimulation session is defined only for 30 minutes, then thestimulation session and associated reminder that were scheduled for thenext day are cancelled.

In an embodiment, the treatment regimen includes an establishedtreatment schedule 302 that is adjusted by a compliance algorithm of thecompliance module 200 as realized by the compliance and non-complianceoperations 307 a, 307 b and also by evaluation of patient input datarelated to symptoms. The evaluation of symptoms occurs in step 313,which provides status on symptom presence, absence, or severity. Forexample, in the presence of symptoms or if severity is above a selectedamount then an induction treatment schedule may be extended and longerstimulation sessions may be used. Alternatively, in the absence ofsymptoms or when severity is less, the treatment schedule defined forvarious treatment events can be made less frequent and sessions may beset to 30 minutes. A change in symptoms reflected by a change scorecalculated as the amount of improvement or worsening of at least onecurrent symptom score compared to a reference symptom score (such as abaseline score assessed at start of therapy) may also cause anadjustment of the treatment schedule 302 according to treatment regimenrules with respect to a duration or dose of stimulation scheduled to beprovided within a defined interval. This can also cause a change in thecriteria and rules used during compliance assessment 304.

In an embodiment, notification signals provided to a user as part ofstep 318 occur according to at least one notification rule that is setin relation to a defined neurostimulation schedule with dates and times.Alternatively, an adjustable neurostimulation schedule is used which isadjusted as a function of elapsed time since a prior treatment. Theschedule may also be adjusted due to symptom severity, with more orlonger sessions scheduled for more severe symptom scores or less/shortersessions scheduled after a symptom improvement above a selected leveloccurs. The schedule can also be adjusted due to an evaluation of thehistory of neurostimulator usage in relation to meeting a dosecriterion. The notifications based upon treatment schedule are adjusted,for example, as a function of elapsed time since last treatment and ascore calculated upon patient input data about symptoms that serves as aproxy for presence, absence, or size of symptom improvement.

In an embodiment, the notification that is provided to a user accordingto at least one notification rule occurs at times defined to be at,prior to, or after dates and times when stimulation is scheduled.Alternatively, the notification occurs at a user-selected,doctor-selected, or default setting which is an interval that occurbefore, or after expiration of at least one inter-treatment intervaldefined in the treatment regimen. When notification occurs after missingthe scheduled treatment session, this is prompted by failure to providethe stimulation within a selected time after the scheduled day and time.

In an embodiment, the treatment schedule is adjusted by a treatmentregimen algorithm using patient input data that is received within adefined interval. The patient input data is compared to data obtainedduring a reference interval about a subjective score, for example,related to symptoms. The adjustment is defined in a look-up table 350 ofthe control module for symptom improvement, no change in symptoms, andsymptom worsening. For example, in look-up table 350 the treatmentregimen allows for adjustment of the treatment schedule from 7 days aweek to 3 days a week at either 4 or 8 weeks if a quality of life scorehas improved by at least 20 or a bladder diary score has improved by 10.

In an embodiment the compliance module is configured to calculate ameasure of compliance in steps 304 or 312 over at least one intervalsuch as a day, several days, a week, a month, a year, since thebeginning of therapy, or other interval of interest (e.g. duringinduction or maintenance, etc). Appropriate criteria are used todetermine compliance for these different periods such as criteriadefined for daily compliance, nightly compliance, weekly compliance,monthly compliance, induction compliance, etc. The notificationsprovided in step 318 are contingent not only on compliance measurements304 but also upon a schedule that is adjusted as a function of time(e.g. more notifications may occur earlier on in the therapy regimensuch as during induction or as a function of symptom severity. Inaddition to the notification schedule, the notifications content beadjusted as therapy progresses or based upon symptoms or symptomchanges, with respect to obtaining patient input about various aspectsof symptoms. For example, if a patient does not indicate a symptomrelated to nocturia, or the answers consistently do not reflect achange, then a notification rule can cause questions about nocturia tobe removed from those presented to a patient. Alternatively, thenotifications provided to a user may be adjusted to be more relevant toa user and may promote relevant patient behavior. For example, ifnocturia is a symptom, then notifications can be sent about going to thebathroom before bed.

In an embodiment, the user notification module 360 is configured providenotifications related to prompting or reminding selected user behaviors.The notifications for treatment of OAB include, for example, remindersto: attempt voiding before an event such as leaving the house or goingto bed; performing pelvic floor exercises; reduce fluid intake; reducefluid intake after a certain time such as during the evening: takemedication; and, provide user input data relate to objective orsubjective measures such as symptom severity. In the treatment ofvarious disorders, the severity of a measure may be related to relatedto overactive bladder symptoms, anxiety, depression, or both. User inputrelated to objective measures may include input of a measurement such asblood pressure if the system is not able to sense this measurementautomatically, for example, using a device incorporated into asmartwatch-like form factor that is worn by a user (e.g., Samsung GearX, Omron HeartGuide) or other manner.

In an embodiment, the treatment regimen or compliance criterion definedfor the provision of neurostimulation is modified based upon a user'scompliance for the provision of medication. For example, if a patientshows increasing non-compliance for a medication then the dose ofstimulation can be increased to compensate. Unlike medication,increasing the dose of stimulation may be accomplished without causinglarge side-effects. While a patient should not typically take 5 doses ofmedication on a particular day if they missed taking a medication daily,providing 5 hours of stimulation instead of one can be done to attemptto compensate when a user does not provide a daily course ofstimulation. Likewise, increasing peripherally supplied stimulationduration may be helpful when users fail to be compliant with medication.Similarly, a treatment regimen or compliance criterion for providingmedication treatment according to a medication treatment schedule may bedecreased based upon neurostimlaution dosage provided over a selectedinterval and/or an assessment of compliance related to the provision ofan ongoing course of neurostimulation, and or assessment of symptoms. Inother words, the provision of more stimulation can entail a decrease oreventual stopping of a medication dose, as long as symptoms do notworsen. Although the dose of stimulation may be increased, clearly withrespect to duration or number of stimulation sessions and less so foramplitude, an upper limit to stimulation may be used simply to deterside-effects such as skin irritation and accordingly the compliancemodule 200 is configured to operate to assess 304 and realize compliancerestrictions to deter this. These restrictions are defined according tointerval rules and preventing the provision of stimulation during asingle session or across sessions from exceeding a defined durationwithin a selected interval. The restrictions can be defined and assessedin step 304 using interval-strength rules that take into accountamplitude and do not permit a user to provide a dose of stimulation thatexceeds a defined maximum dose within a selected interval. In the caseof non-compliance the operation 307 b causes the neurostimulator to bedeactivated and a message provided to a user 318 disclosing the reasonfor this action.

Alternatively, the notification is sent 312 to a remote clinic or doctorcomputer 71 using a communication module so that compliance can beassessed, and the doctor may choose to increase the maximum allowablestimulation dose after talking with a user. The neurostimulator oruser/physician programmer 70 or other system component is configured sothat parameters are adjusted in the treatment regimen and compliancemodule 200 by clinician using a clinic computer. Other types ofnon-compliance may be defined to cause the system to restrict use. Thecompliance module 200 is further configured to operate according tocompliance rules that are defined to cause the compliance module tocause the control module to disable the stimulation operations providedby a stimulation module 54 of the neurostimulator if at least onecompliance criterion is assessed as false because the criterion was notmet. At home therapy requires the cooperation of a patient, and use canbe restricted, for example, if a user fails to provide patient inputdata about symptoms so that therapy benefit can be tracked accurately bya physician monitoring a user remotely. Accordingly, the compliancemodule is further configured to operate according to compliance rulesdefined for non-compliance operations 307 b that cause the notificationmodule to communicate a notification signal 318 to a computer operatedby third party such as a doctor or medical monitoring service if thepatient does not meet at least one selected compliance criterion.

In line with the need to have a user actively participate during at-hometherapy, the compliance module 200 is further configured to operateaccording to compliance rules in the non-compliance operations 307 bthat cause a restriction in the user/programmer 70 that withholdspermission of communication with, or provision of stimulation by, aneurostimulator until selected outstanding or omitted user input data isreceived. The user input data may include, for example, one of thefollowing: input data related to presence, absence, or severity ofsymptoms; input data related to information scheduled to be input by auser; input data including an activation code provided to re-activatethe system after a flag status has been set to false (the patient wasnon-compliant for treatment or subscription/token payment); input datarelated to a code on a disposable stimulation pad; and, input datascanned in or received by RFID or otherwise for a system component ordisposable.

When a user schedules at least one treatment event such as a session (byselecting a day of the week, time, and treatment duration that serves asa recurring scheduled treatment of the treatment regimen) then thecompliance module compares treatment event history against the treatmentregimen to determine compliance 304. The system can be configured toquery a user to select the parameter for a recurring scheduled treatmentwhen the systems is first used by a user, or at a time thereafter. Theestablishment of a treatment regimen 302 and monitoring of compliance304 may be done using a treatment regimen that is defined for animplanted neurostimulator, an external neurostimulator, or thecombination, as may be defined by selecting appropriate controls 180. Inthe case of combination treatment using more than one neurostimulatorsuch as an implanted and external treatment regimen, the compliancemodule calculates compliances for a treatment schedule which includesthe combination of a first treatment provided by at least oneimplantable neurostimulator and at least a second treatment selectedfrom the group of: treatment provided by a percutaneous neurostimulatorwith a needle stimulator; treatment provided in conjunction with anintravaginal stimulation device; treatment provided by a magnetic pelvicfloor stimulation device; treatment provided by a transcutaneouselectric or magnetic stimulator; treatment provided by a pelvic floorstimulator; treatment provided by pharmaceuticals as may be indicated byat least one of: patient input, electronic tracking or communicationrelated to the provision of pills, delivery of injected drug, cutaneousdrug delivery systems, drug eluting patches, or implantable drugdelivery. The compliance module can be configured to adjust the secondtreatment schedule based upon provision of the first treatment, orvice-versa. For example, if an external treatment is provided thatexceeds a defined dose then the implanted treatment schedule may beadjusted to provide a decreased dose of stimulation. In this manner, ifthe user provides sufficient stimulation by an external stimulator thenthe implanted neurostimulator 300 can save battery by decreasing itsstimulation. The implantable neurostimulator can serve as a back-up if auser fails to provide sufficient stimulation using an externalneurostimulator.

In an embodiment, the notification signal provided in step 318 is anauditory, visual, textual, vibrotactile, or multimedia message providedby the notification module 360 or is a digital signal transmitted bywired or wireless protocols of the communication module 68. Thenotification step 318 can also include accepting user input in responseto the notification and operating based upon the user input data. Thenotification module 360 is configured to interact with a communicationmodule 68 which communicates with voice service technology such asAlexa™. In turn, the voice service then operates at pre-defined times tocause notifications to be provided using either auditory notificationsignals over its speakers or visual notification signals, or both. Forexample, the voice-service may present a message to a user using a smartappliance such as a smart-TV, user smartphone, smartwatch, or othersmart interface. The voice service technology is also configured toreceive a user vocal response or other user input (e.g. responseprovided using a gesture sensed by a video camera of a smartphone) thatis provided in response to the notification. In an example, at least oneof the following responsively occurs during the notification operations:the user is asked and answers a question prompted by the voice-servicewithin a selected interval or the user is notified stimulation isscheduled to occur and confirms or rejects this beginning of a treatmentsession; the user provides a verbal instruction that controls therapy bycausing the voice service technology to transmit or control thetransmission of a command signal that is intended for reception by anexternal user/physician programmer 70, system component, or external orimplanted neurostimulator; and, the user provides vocal instructionsthat are received by the voice service technology which instructs thesystem to provide an additional reminder at a future time when theelapsed time since last stimulation treatment exceeds a clock valuemeasured by the control module 52.

In an embodiment, the compliance module is configured to maintain ahistorical record of treatment events, parameter values, and compliancestatus flags and states that are related to assessing compliance. Itevaluates the historical record using at least one compliance criterion304 that can assess compliance for a treatment event type across aselected interval such as weeks, months, etc. The historical recordincludes information such as: parameters of stimulation treatment thathas been provided; treatment events provided according to a treatmentschedule; user behavior (e.g., drinking, voiding) and user activity(e.g., sleeping, walking) data obtained by user input or sensing; othertypes of user input data and sensed data; and, a history of treatmentevents such as notification messages provided to a user.

The compliance module is configured to use the historical record totrack compliance over time to generate summary statistics and trendgraphs. Assessing the log history allows determination of whether apatient meets at least one compliance criterion related to multipletherapy events. The historical record is used for adjusting a treatmentschedule and similarly adjust the compliance rules and criteria used toassess compliance in relation to the schedule or used for selectingcompliance criteria from a lookup table and is used to calculate anddisplaying statistics related to at least one compliance measure 312.The historical record can also be used to adjust notification parametersrelated to the provision of notification defined in relation tosuccessfully meeting or failing to meet at least one compliancecriterion.

For example, if a history of non-compliance for a treatment event isdetected, the notifications can be increased for that event. In anembodiment, a notification parameters and rules look-up table 352 ofFIG. 18 dictates that the maximum number of reminders that occur if theprovision of stimulation does not take place is 3. If evaluation of ahistorical record of compliance determines that the patient isnon-compliant for providing stimulation during (e.g., non-compliance hasoccurred for at least 4 of the prior 8 weeks) then the maximum number ofreminders sent due to a missed treatment session can be increased to 5.

Table 352 of FIG. 18 shows an illustrative embodiment of notificationparameters and rules. For example, during induction notifications aresent 15 minutes before a treatment session is scheduled to occur. If theuser does not provide the treatment at the scheduled time then anotification is sent 1 hour afterwards. The notification provided toalert to an upcoming session includes a text message displayed by theneurostimulator or user/physician programmer 70 or other systemcomponent. The notification sent if the stimulation does not occurincludes both text and auditory signals. A notification rule dictatesthat the notification occurs a maximum of 3 times, unless the patienthas been non-compliant for at least 4 of the prior 8 stimulationsessions, in which case the maximum number of reminder alarms isincreased to 5. The permissions is set to “All” which indicates thateither the doctor, patient, or caregiver may adjust the parameters ofthe notification rule. In this example, the notification rule forsurvey/diary events is set to “text+tone+voice” indicting that if thepatient is at home that notification will be provided using text, sound,and also through communication with a voice service if available. Inthis example, the notification for disposable pad replacement mayinclude these same notification types but additionally includenotification in a shopping cart feature of the ecosystem provided by adigital shopping cart module 364.

Therapy Gamification

In an embodiment, the treatment regimen is realized within a gamestructure. “Gamification” of the therapy includes providing game-likerewards, punishments, and experiences as part of the therapy regimen topromote improved compliance, user interest, and fun. Similar to a game,points may be gained or lost depending upon how well the user “plays thegame” which in this case is being a compliant patient and performingbehaviors that increase therapy benefit. The rules of the game and pointallocations are defined in the regimen, defined by the patient, ordoctor depending upon various factors. For example, a doctor may assigna point value to a behavior the has been found to improve therapyoutcome in a group of patient or which is designed to cause increasedcompliance of a behavior for the patient. A scoring method andassociated look-up table of points to be used during treatment are shownin FIG. 19 and FIG. 20, respectively.

As shown in FIG. 19, in an embodiment a neurostimulation gamificationsystem has at least a first processor of a control module 52 that isconfigured for operating a gamification module 370. The gamificationmodule is configured for retrieving the score and score history of auser 330 which may be invoked by step 322 implemented by the compliancemodule, invoked directly as part of step 303, or otherwise by thecontrol module 52. In step 332, treatment events are assessed. Thisassessment can include sensing, detecting, registering, tracking,monitoring, and assessing treatment events that have occurred as well asthe event characteristics. The score subroutine also assesses treatmentcompliance measurements and metrics 334 as well as any flags states thatare set as part of step 309. In the next step, the event and compliancedata results obtained in steps 332 and 334 are analyzed in step 336which uses score rules having score criteria to derive score points thatresult from implementing the score rules. In the next step scores areupdated 338, by adjusting at least one score according to at least onescore rule based upon event data. This may include updating a globaltreatment score as well as scores related to treatment events (providingstimulation, answering survey questions provided by the system),compliance, timely replacement of disposables, and use of ecosystemfeatures such as videos, virtual meeting with medical professionals,etc. The score rule calculations use event data measures and associatedflag states which reflect for example event occurrence, event absence,event count, and at least one characteristic of an event. The score rulecan assess event data in relation to a characteristic of a programmabletreatment regimen such as compliance for a schedule of treatment events,using the data from step 334. In the next step 340 the score history logis updated with any changes to scores as well as the reasons for thechanges in points (i.e. the results of assessing the different scorecriteria are stored in addition to the changes in points so that thereasons for the score changes can be reviewed by a medicalprofessional). In step 342 score contingent operations occur. Forexample, a score is displayed on the housing of a neurostimulator, or isupdated on the display of an external patient controller 70 configuredto display information including at least one score associated with agame to a user, accept user input, and to communicate data to and fromthe at least one neurostimulator 52 a that is functionally coupled to aprocessor of the control module 52. Other score related contingentoperations may be alerting the user that they have won a symbolic awardsuch as a gold star, or “good patients” status. Another score contingentoperation can be alerting the user that they have obtained a discountthat may be applied to the cost of the treatment or disposables.

In embodiments, a score contingent operation may result in the userobtaining a reward realized as a real-world reward. For example, if theneurostimulation treatment is related to a weight management program,and the user has been compliant with stimulation, then the system canauthorize a dessert to be included in the next order of food from a foodplan delivery service that is part of the weight management program. Inanother example, in the treatment of a psychiatric or other disorder,the score results in credit that provides access that allows a user toplay a selected video game over the internet for a selected period toprovide an incentive when the system is used to provide treatment inchildren, teenagers, and in cases of treatment of addiction.

FIG. 20 shows an example of a portion of a look-up table 354 that isused by the score rule to determine the points that are used to change auser's score. There are points defined for treatment behavior related tothe provision of neurostimulation treatment which include providing a 2point bonus of the user provides treatment within 1 hour from the timethe user is alerted about a scheduled treatment session. Failure toprovide the treatment in a timely fashion results in a 1 pointdecrement. In this example the treatment session is defined as 30minutes of stimulation, and the user obtains additional points forstimulating for at least 60 minutes or over 2 hours Failure to stimulatefor longer than the defined treatment session does not result in anypoint decrement. Points are also obtained for providing one quality oflife set of questions per week, completing one digital bladder diary permonth, and answering a short symptom survey on a daily basis. Thebladder diary completion results in greater point change because itrequires more effort from a user. The symptom survey results in a smallincrease in points because it is easy, but a larger decrement toincentivize users to complete that task since it is simple and allowssymptom changes to be tracked on an ongoing basis. Points are alsodefined for ecosystem features such as watching videos related to theprovision of treatment of lifestyle changes, or using digital softwaretools such as participating in (leaving comments) in an online communityusing a software application of the system or conducting avirtual-meeting with a nurse-practitioner who can review the treatmentprogress with a user and answer questions, etc. Point additions anddecrements are also defined for replacement of disposable systemcomponents according to a defined schedule or number of uses. The valuesshown are simply for illustration and can be adjusted by a user, doctor,caretaker, or otherwise in order to promote therapy compliance andbehaviors that increase the chance for therapy benefit. The score rulesaccess the point values during their implementation.

In example embodiments, the gamification module 370 is configured forassessing a treatment event by sensing a treatment event (e.g. operatingwith a sensing module 55 to determine that a blood pressure reading hasbeen obtained or assessing IoT sensor information to determine if a userhas gone to the bathroom), detecting a treatment event (e.g. operatingwith a stimulation module 54 and detecting that a neurostimulationsession has been carried out by a user), registering a treatment event(e.g. operating with the survey module 61 to determine the a user hasanswered a set of survey questions), tracking treatment events (e.g.assessing if a user has consistently provided above a minimum number ofstimulation treatments over a prior period of a month), monitoringtreatment events (e.g., communicating with a voice services device tomonitor that a user has provided user information to the voice servicesystem that is relevant to treatment events), and assessingcharacteristics of treatment events (e.g. determining the duration of atreatment session) that have occurred and adjusting at least one scoreaccording to at least one score rule based upon event data. For example,a score rule can assess event data by evaluating two characteristics oftreatment events according to two score rule criteria. The firstcriterion of the score rule evaluates if a selected number of minimumtreatment sessions have occurred for a prior period such as 1 week andthe second criterion assess total treatment time for the last week asbeing over a selected amount. The rule dictates that if the firstcriterion of the score rule is not met then the score is decremented by1 point, unless the second criterion exceeds an amount such as 2 hours.Accordingly, if the user provided 3 treatment sessions of 2 hours, 30minutes, and 25 minutes, then if the first criterion requires 3 sessionsof at least 30 minutes each, then this will not be met. However, sincethe user provided a 2 hour session, the second criterion is met. In thisexample, score rule results in no decrement to the score, but also noincrement since the 3-session criterion was not met. Score rule#1: Ifscore rule #1 criterion #1 is met (# complete treatment sessions fordefined interval >2) then increment treatment score by 1 point(treatment score=treatment score+1); AND If score rule #1 criterion #1is not met (# complete treatment sessions <3) then decrement treatmentscore by 1 point (treatment score=treatment score−1); AND If score rule#1 criterion #2 is met (total treatment time for defined interval >2hours) then increment treatment score by 1 point (treatmentscore=treatment score+1).

In an embodiment, a neurostimulation gamification system comprises afirst processor configured for operating a gamification module 370 undercontrol of a control module 52, and a neurostimulator coupled to theprocessor for control and communication related to the provision ofstimulation as part of a therapy regimen. The gamification module 370 isconfigured for registering and assessing therapy events that haveoccurred or failed to occur and adjusting at least one type of scoreaccording to at least one score rule. The calculation of scoreadjustment occurs using points derived by evaluation of compliance andevent data such that the scores reflect therapy event occurrence,absence, and count. The scores can also be adjusted based upon acharacteristic of an event (e.g. duration of a stimulation session), andassessment of event data in relation to a characteristic of aprogrammable treatment regimen, which may be assessed with respect tocompliance or otherwise. The system includes an external patientcontroller 70 configured to display scores, information related to thescore, and other features of a game that is designed to reflect therapystatus and progress, as well as user compliance. The external device 70is also configured to accept user input data and to communicate data toand from the at least one neurostimulator.

In embodiments, the scores result in promotion to a higher status levelin a manner that is fun, funny, or amusing to a user. For example, inthe treatment of overactive bladder, as a user's score increase, theirstatus may increase from, for example, “Peon of Pee”, “Serf of Pee”,“Pee Apprentice”, “Knight of Pee”, “Pee Warrior”, “King of Pee”, towarda top status of “Emperor of Pee”. For a female user the status can beadjusted to “Queen of Pee” etc. As points accumulate, higher status, newgame levels, and options unlock. As part of the “Sapho” online communityscoreboards or “leader boards” may be shown with individuals whocollected the most points. When used in the treatment of disorders suchas children with depression or autism, symbolic status may be a serve asa good incentive.

In embodiments, increases in score result in rewards having a symbolic,virtual, or monetary value, or associated with a monitory discount,coupon code, or reward/loyalty points. For example, if the system isconfigured to provide neurostimulation only when a treatment credit orsubscription is active, and this requires a monthly payment, thenimproved compliance may result in a score increase that leads to acoupon code. The code may be applied directly to a shopping cart module364 of the system.

In embodiments, the adjustment of at least one score by the gamificationmodule occurs according to at least one score rule that assess eventdata and occurs using parameters of a lookup table 354 having positiveand negative points that are used to change the score. Score algorithmsinclude formulas and rules that may limit adjustment of a score. Forexample, the score algorithm may restrict a maximum increase in pointsfor a particular therapy event type. This serves to inhibit a user fromgaining points through frequent interaction with an online communityusing the social app of the system, while failing to be compliant forother therapy event types. Restricting points for event types provide anincreased balance to how points are awarded by the system. The pointsshown in the table are examples, and can have programmable point values,where larger values are set by a doctor or patient based upon eventsthat have greater importance to treatment. Point maximums may also beapplied to usage data related to a patient providing neurostimulationwherein the usage data is assessed by integrate the amount ofstimulation time or dosage that has been provided across a selected timeinterval. In this case, the total amount of points obtainable byproviding many hours of treatment is restricted and cannot substitutefor a user being compliant to other therapy event such as providingelectronic survey data about symptoms. The scores can also be adjustedaccording to points associated with a measurement of compliance, and theadditional of points may be restricted if a measurement of compliancedoes not meet a treatment criterion.

When the gamification module is configured for adjusting at least onescore calculated based upon the user providing neurostimulation which isassessed in relation to compliance with respect to a defined stimulationschedule, then points are rewarded for adherence to this schedule.Alternatively, there may be no schedule defined and the treatmentcriterion may simply be that the user provide stimulation at least every2-3 days and the score value is calculated based upon assessment ofelapsed time between stimulation sessions being less than a selectedamount. As shown in the table 354, points can be allocated when anotification is provided to a user that stimulation should occur and theelapsed time between the notification and when the stimulation isprovided by the user is below a selected amount.

When scores are adjusted based upon compliance with treatment events,points can be allocated to adjust at least one score based upon the userproviding or failing to provide answers to at least one set ofquestions. Further the points may be increased if the user opts toanswer a larger set of questions since that will provide a more completeassessment of patient benefit. The points can be allocated based uponcompleteness of, for example, the user inputting data to a bladder diaryor completing items of a quality-of-life survey instrument, with respectto the timing and completeness of the user input data and the scheduleof when these data to be input by the user.

As shown in table 354, in the category treatment, the gamificationmodule is configured for adjusting a score if the user providestreatment within an elapsed time from receiving a notification that atreatment session is scheduled. Further, the gamification module isconfigured for adjusting at least one score based upon the patientproviding additional stimulation treatments that exceed a definedtreatment program that has been curated to provide a minimum doserequired for induction or maintenance of therapeutic benefit. In thiscase providing a stimulation session of at least 1 hour results in animproved score, with a further point reward if that exceeds two hours.

As shown in Table 354, in the “behavioral category” the scoringalgorithm of the control module is configured for adjusting at least onescore based upon the patient providing adjunctive therapy such as pelvicfloor exercises, as may be registered in the system by user input. Ifthe user learns about pelvic floor exercises by watching videos thepoint gain is higher since this is being rewarded as a more importantbehavior. Additionally, the gamification module is configured foradjusting at least one score based upon the patient input data assessedas positive defined lifestyle changes such as reducing amount of coffeeintake per week. The gamification module is also configured foradjusting at least one score based upon assessment of the patient inputdata in relation to the user following a doctor's orders such asperforming kegal exercises a minimum number of times per week. Thegamification module is also configured for adjusting at least one scorebased upon scheduling and participating in web-based meetings withmedical support staff to review treatment progress and answer questionswhich in the table is rewarded with 7 points since this is encouraged.Although not shown in the table, the gamification module is alsoconfigured for adjusting at least one score based upon the complianceof, or frequency with which, the user provides input related to sensordata such as results of testing the user's blood pressure. Although notshown in the table, the gamification module 370 is configured foradjusting at least one score based upon compliance to a medicationtreatment regimen which may be obtained by a review of user input dataor sensed data about medication delivered to patient orally, byinjection, dermally applied, applied via a patch or otherwise.

In an embodiment, the gamification module is configured for adjusting atleast one score based upon analysis of data input by the patient orsensed by the system about timely replacement of disposable componentsaccording to a schedule and/or regularly recharging a battery of theneurostimulator.

In an embodiment, the gamification module evaluates at least one scorethat is calculated in relation to at least one score criterion todetermine discount or rebate on at least one payment related to cost ofdisposable products, a monthly subscription payment, insurance, and/ormedication. The discount can be provided by providing a user with anelectronic credit token or discount code or coupon that is only operableor accepted by the neurostimulation system that is associated with theuser. A reward may also be provided as positive benefit, reinforcementof behavior associated with good therapy outcomes which is selected tobe increased insurance coverage terms or an extension of a period ofservice coverage or subscription period. Alternatively, a score can beassessed in relation to at least one score criterion to provide apunishment in the case of non-compliance such as increased cost ofco-pay, revocation of coverage, denial of coverage, and change inpatient status such as a ranking or status within the game environment.The present score of a patient can be assessed by the gamificationmodule in relation to at least one score that is evaluated in relationto at least one score criterion and results in the user earning scorepoints, award badges, improved patient status. The gamification modulealso can present the current score and progress graphically to patientsso that they can view their progress toward achieving at least onetreatment goal set for the patient. The graphic presentation may alsoprovide a table of rewards that are contingently tied to theaccumulation of points. Treatment goals may be defined for the patientand related to various treatment event types such as user adherence tothe provision of treatment according to a regimen, compliance withanswering survey item data, provision of sensed data with the assistanceof the user, and other treatment event types.

In embodiments, the compliance module, gamification module, and othermodules of the system are related to the provision of therapy regimenwhich includes using an external neurostimulator or controller in thetreatment of disorders including for example, migraine, headache,depression, pain, a sleep disorder, insomnia, a psychiatric disorder, ananxiety disorder, an unwanted medical condition, disorder, or patientstate, a movement disorder, tremor, a cardiovascular disorder, a bloodpressure disorder, arrhythmia, a disorder which is treated by modulationof the vagus nerve, median nerve, and/or a disorder treated bystimulation of a nerve of a lower limb of the patient. Additionally, thetreatment may also be related to at least one of: addictions, substanceuse disorder, opioid use disorder, insomnia, psychiatric disordersincluding depression, schizophrenia, anxiety, traumatic brain Injury,epilepsy, a cognitive disorder or unwanted cognitive state, Alzheimer's,dementia, PTSD, movement disorders, Parkinson's, multiple sclerosis,Autism Spectrum Disorder, attentional disorder, oncology disorder,inflammation, and gastrointestinal, cardiac and respiratory disorders.The system can also be used to promote a healthy state, to improveperformance, or during rehabilitation. For example, an athlete can usethe system using during training to improve performance or forrehabilitation from injury. While not treatment a disorder such asstroke, the system can be used to assist with recovery of function.

The modules described for the apparatus 50 are for illustration purposesonly and the subject invention can have less than or more than themodules and system components described in this specification, or can berealized in alternative embodiments. For example, rather than having aprotocols and parameters module 66, the information related tostimulation protocols and parameters can be simply stored in the memorymodule 60. Disclosed components and modules may be omitted and modulesmay communicate with, and share, resources of other modules. Any of thesystem components or modules can be realized partially or fully in thephysician/patient programmer 70, remote computer 70′, orneurostimulation system 50. The modules may reside within the device 50housing or may exist externally and communicate. The apparatus 50 may berealized as a portable or desktop instrument that controls accessories.The system can be implemented, at least in part, as customized hardwarethat operates with a smart-phone or tablet computer or whichcommunicates with the smartphone or computer so that some disclosedmodules are realized by the smart phone or computer.

The subject systems and methods may be realized using variousinstruments and tissue stimulators patented and/or distributed bycompanies such as Cogentix, Electrocore, Cyberonics, Medtronic, ValenciaTechnologies, StimGuard, Halo Neuroscience, eNEURA (e.g., TMS), Bioness,and Cephaly, for providing stimulation of human tissue. This includeselectrical, magnetic, microwave or other forms of energy directed eitherto implantable components that stimulate tissue or to the tissue itself.This can include cranial electrotherapy, transcranial stimulation (e.g.,direct-current or alternating current), ultrasonic neuromodulation.Stimulation provided by at least one of TENS, eTENS, percutaneous,external, partially or fully implantable systems can be operated toprovide stimulation using the protocols and nerve targets disclosedherein. Patients (including children with urinary disorders) may betreated with either TENS, percutaneous, or implanted devices as a meansof reducing their OAB symptoms that include incontinence, enuresis, andnocturia, or treating various pelvic floor disorders by SAFNstimulation.

Embodiments disclosed herein for treatment of OAB are applicable totreatment of specific symptoms and disorders such as incontinence, urgerelated to and frequency of urination, bladder pain, fecal incontinence,sexual disorders, and pelvic floor disorders and their symptoms.Treatment can include relief from symptoms, improvement of abnormalactivity, etc.

In the specification, section titles are provided for convenience onlyand are not meant to limit the invention. Methods disclosed hereininclude method steps, but these steps and the related operations may beomitted or occur in a different order during operation of the system.

The foregoing description of preferred embodiments for this disclosurehave been presented for purposes of illustration and description. Theyare not intended to limit the invention to the precise forms disclosed.Obvious modifications or variations are possible in light of the aboveteachings. The different embodiments are chosen and described to providethe best illustrations of the principles of the invention and itspractical application, and to thereby enable one of ordinary skill inthe art to utilize the invention in various embodiments and with variousmodifications as are suited to the particular use contemplated. Allthese modifications and variations are within the scope of the inventionas determined by the appended claims when interpreted in accordance withthe breadth to which they are entitled.

We claim:
 1. A treatment regimen compliance system comprising: at leasta first processor configured for operating a control module; at leastone neurostimulator coupled to said at least one processor andconfigured to communicate data or control signals to and from the atleast one first processor; the control module configured to establish aprogrammable treatment regimen and control a compliance moduleconfigured for calculating a measurement of compliance for at least onecharacteristic of the programmable treatment regimen, the programmabletreatment regimen defined for at least one neurostimulation provided byat the at least one neurostimulator; at least one user notificationmodule coupled to the control module and configured to send anotification signal to a user related to compliance of the programmabletreatment regimen, the notification signal sent being responsive to atleast one notification rule; and, at least one externalpatient/physician device configured to present notification signals,accept user input data, and communicate data or control signals with theprocessor.
 2. The system of claim 1, wherein said notification moduleoperates at least partially under control of the compliance module basedupon at least one parameter defined for treatment regimen operations. 3.The system of claim 2, wherein said at least one parameter defined fortreatment regimen operations includes a defined dose of stimulation tobe provided within a selected time interval.
 4. The system of claim 2,wherein said at least one parameter defined for treatment regimenoperations includes a defined set of questions to be to be provided andanswered within a selected time interval.
 5. The system of claim 2,wherein said at least one parameter defined for treatment regimenoperations includes a defined set of training videos to be to be viewedwithin a selected time interval.
 6. The system of claim 2, wherein saidat least one parameter defined for treatment regimen operations includesa defined set of messages about lifestyle changes to be to be viewedwithin a selected time interval.
 7. The system of claim 1, wherein themeasurement of compliance of at least one characteristic of aprogrammable treatment regimen related to the at least oneneurostimulation defined for the at least one neurostimulator, includesdetermining if a compliance criterion has been met which includes aminimum stimulation dose delivered across a selected time interval. 8.The system of claim 1, wherein the measurement of compliance of at leastone characteristic of a programmable treatment regimen related toneurostimulation defined for at least one neurostimulator, includesdetermining if a minimum number of treatment sessions lasting minimumdefined period of 30 minutes have been delivered within a selectedinterval.
 9. The system of claim 1, wherein the notification rule, ormeasurement of compliance of at least one characteristic of aprogrammable treatment regimen related to neurostimulation defined forat least one neurostimulator, includes at least one of: a. determiningif a maximum number of treatment sessions lasting a minimum definedperiod have been delivered within a selected interval; b. determining ifa maximum defined dosage has been delivered within a selected interval;c. determining if a user has alternated stimulation sites between thetwo sides of the body or two sites after a selected interval ofstimulation, as defined by a stimulation location criterion; d.determining if a user has replaced disposable stimulation pads within aselected interval, as defined by a replacement of disposables criterion;e. determining if a user has scheduled a doctor visit at a clinic orvirtually using a web-meeting medical assistance module within aselected interval, as defined by a check-up criterion; f. determining ifa user has performed a minimum number of defined behaviors such as suchas kegal exercises, electrically assisted intravaginal stimulation,within a selected interval, as defined by a check-up criterion; g.determining if a user has been compliant with respect to a medicationregimen that is intended to occur over the same time period as theneurostimulation, as defined by a medication criterion; h. determiningif a user has been compliant with respect to a digital health regimenthat includes being engaged daily or weekly using digital health toolprograms, as defined by a digital health tools criterion; i. determiningif a user has been compliant with respect providing stimulation withinselected intervals of scheduled treatment times, as defined by a latencycriterion; and j. determining if a user has been compliant with respectproviding stimulation according to a minimum number of scheduledtreatment times that occur at night, as defined by a therapy criterion.10. The system of claim 1, wherein the measurement of compliance of atleast one characteristic of a programmable treatment regimen related toneurostimulation defined for at least one neurostimulator, includesdetermining if a compliance criterion has been met for at least onestimulation session and graphically displaying a status related towhether the criterion was met or not.
 11. The system of claim 1, whereinthe measurement of compliance of at least one characteristic of aprogrammable treatment regimen related to neurostimulation defined forat least one neurostimulator, includes determining if a compliancecriterion has been met relating to a treatment regimen operationoccurring contingently based upon at least one of the following:according to a calendar schedule, according to the presence, absence,severity, change, or trend of patient symptoms evidenced by evaluationof a history of user input, according to both a calendar schedule andevaluation of user input data from a previous period.
 12. The system ofclaim 10, wherein the treatment regimen operation includes receivinguser input data to 1 or more questions contingently presented to a user.13. The system of claim 1, wherein the compliance module is realized asat least one of: a module of the at least one neurostimulator, andmodule of the at least one patient/physician device, or as a modulerealized distributed across the at least one neurostimulator andexternal patient controller.
 14. The system of claim 1 wherein thetreatment regimen includes a treatment schedule that is adjusted by acompliance algorithm of the compliance module using patient input dataconcerning least one of the group of: symptom presence, absence,severity, or change reflected by a change score calculated as the amountof improvement or worsening of at least one current symptom scorecompared to a reference symptom score, a duration or dose of stimulationprovided within defined interval, and elapsed time since laststimulation treatment.
 15. The system of claim 1 wherein notificationsignals are provided to a user according to at least one of: a definedneurostimulation schedule, an adjustable neurostimulation schedule thatis adjusted as a function of at least one of the following: elapsedtime, symptom severity, neurostimulator usage.